Injured tissues can be repaired and damaged organs healed using a new nanotech device that adapts a patients own skin to generate stem cells, according to a paper published in the journal Nature Nanotechnology.

Researchers from Ohio State University call the new technology tissue nanotransfection (TNT).

They say TNT which is basically a lab on a chip can adapt skin cells to change into any type of tissue required, which can then be introduced to injured or degenerated areas. They claim a success rate of 98%.

With this technology we can convert skin cells into elements of any organ with just one touch, says co-author Chandan Sen. This process only takes less than a second and is non-invasive, and then you're off. The chip does not stay with you, and the reprogramming of the cell starts. Our technology keeps the cells in the body under immune surveillance, so immune suppression is not necessary."

Lead author Daniel Gallego-Perez says the new technology comprises two elements: the nanotech chip designed to introduce reprogrammed DNA into existing adult cells; and a specific biological cargo that induces the cells to change from one type to another.

The device works using a small electrical charge.

It does not require any laboratory-based procedures, according to Gallego-Perez, and can be used at the point of care a doctors office, say, or an outpatient clinic.

The paper describes experiments on mice and pigs. These included using the device to act upon badly injured legs that lacked blood flow. One week after the application of TNT, vascular vessels reappeared. Within a fortnight flow was back within normal parameters.

In a second experiment, skin cells were converted into nerve cells and introduced into the brains of mice crippled by stroke.

Says Sen: By using our novel nanochip technology, injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining.

The concept is very simple, adds co-author James Lee: As a matter of fact, we were even surprised how it worked so well. In my lab, we have ongoing research trying to understand the mechanism and do even better. So this is the beginning, more to come.

Lee, Sen and Gallego-Perez were part of a group of researchers that lodged a patent application in 2016 for an earlier iteration of TNT: a device that enables compositions and methods for reprogramming somatic cells into induced endothelial cells.

View original post here:
Nano-chip promises to heal organs at a touch - Cosmos

Skin Stem Cells Comments Off on Nano-chip promises to heal organs at a touch – Cosmos | August 7th, 2017

"By using our novel nanochip technology, injured or compromised organs can be replaced, said Dr Sen.

We have shown that skin is a fertile land where we can grow the elements of any organ that is declining.

TNT extends the concept known as gene therapy, which has been known about for some time, however the big difference is how the DNA is delivered into the body.

"The concept is very simple," said Professor James Lee, who co-led the research.

"As a matter of fact, we were even surprised how it worked so well.

In my lab, we have ongoing research trying to understand the mechanism and do even better.

So, this is the beginning, more to come."

"By using our novel nanochip technology, injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining, said Dr Sen.

The study is published in the journal Nature Nanotechnology.

Read the original:
Penny-sized nanochip pad to regrow organs and heal injuries - Telegraph.co.uk

Skin Stem Cells Comments Off on Penny-sized nanochip pad to regrow organs and heal injuries – Telegraph.co.uk | August 7th, 2017

Nalini Ambady, the first Indian-American woman to teach psychology at three major universities in the U.S., died in 2013 due to leukaemia when she was just 54.

For the medical fraternity in Kerala, her native place, it turned the spotlight on the lack of awareness of stem cell transplant, which could have saved her life.

Four years down the lane, doctors say the situation has changed only marginally, as many patients who require the treatment have not been able to do it because of high expenses, lack of matching donors, and lack of facilities at hospitals.

Doctors note that stem cell transplant is being proposed as an effective treatment for cancers such as leukaemia and lymphoma, and primary immune deficiency disorders. Stem cells do not develop normally in such patients and it affects the blood cells that they make. By a transplant, the patient gets new stem cells that can make new and healthy blood cells. Earlier, stem cells were collected from the bone-marrow. Now, it is being collected from blood cells.

Neeraj Sidharthan, bone marrow transplant physician at Amrita Institute of Medical Sciences, Kochi, told The Hindu that in Prof. Ambadys case, though matching donors were found, they had all dropped out.

Lack of awareness is still a major issue though there are some positive signs. In some cases, because of lack of infrastructure, cancer cases are not being diagnosed early and treatment is delayed too, he said.

Ajith Kumar V.T., professor, department of paediatrics, Government Medical College, Manjeri, said donors could not be found often from the same families because of the nuclear family system.

There are not many places where you can match the human leukocyte antigen (HLA) typing with donors. Another problem is the lack of stem cell registries in the State from where matching unrelated donors could be found.

Even if doctors suggest a stem cell transplant, many families dont opt for it because of the high cost involved. If the donor is from the same family, the cost is relatively low. But for unrelated donors, it is very high, Dr. Sidharthan said. The solution, Dr. Ajith Kumar said, was government intervention to set up HLA registries and bone marrow transplant centres. nestCare Foundation, a not-for-profit organisation based in the U.S., had recently approached us expressing interest to set up these facilities in the State. Talks are on, he said.

A.S. Jayanth

View original post here:
Trust those cells to help cure cancer - The Hindu

Bone Marrow Stem Cells Comments Off on Trust those cells to help cure cancer – The Hindu | August 6th, 2017

Tom Parham remembers the time his Woodrow Wilson baseball team was playing Class AAA power Huntington East.

It was 1980, and the Flying Eagles were hosting the Pony Express at Harry Lewin Field. Not known to be a cavernous venue, the field lent itself to an offensive barrage and Huntington East was the last team standing.

A few weeks later, Parham led Woodrow to the state championship game and a rematch with the Express. Woodrow fell short again, but this time it was by the more purist-friendly score of 2-1.

It was then that Parham knew the Eagles needed a new field.

In stepped Doug Epling, Beckley businessman and community leader. He would later be known for refurbishing the old East Bank High School field for WVU Tech to use, as well as the construction of Linda K. Epling Stadium in Beckley, the home of the West Virginia Miners.

The latter, of course, bears the name of Epling's wife. The Tech field is named for Epling himself.The field he helped build on the Woodrow Wilson campus doesn't have an official name.

That will change Saturday.A ceremony will be held at 2 p.m. in the school cafeteria to officially rename the field for Thomas Parham.

The effort to honor the longtime coach was started by Sheila Brown.

"Words cannot describe how it feels," Parham said. "When Mrs. Brown started talking about it, I always told her, nah (modestly). I just thought, 'Let it go.' And finally she told me in April, 'Well, I'm going to the board. I'm going to ask them.' So she did and they told her what to do (at the next meeting)."

The Raleigh County School Board laid out a plan for Brown, and at the next meeting former coaches, colleagues and friends voiced their support.

Legendary boys basketball coach Dave Barksdale. State championship-winning football coach Pete Culicerto. Fellow New Hope Baptist Church member C.W. Claytor. Even Epling himself. They all showed up to see that Parham got the respect they feel he deserves.

"It was just touching to hear former coaches Coach Barksdale, Coach Culicerto, and I even heard from one of my coaching buddies from out of town, Ron Rose," Parham said. "He told Pete what (he wanted) to say. It was just touching, and a humbling experience."

Parham is being recognized for a career that spanned nearly three decades. He was hired as a biology teacher by Ross Hutchens before the start of the 1974-75 academic year.

"He said, 'I need a good biology teacher. I can get a coach anywhere,'" Parham said, laughing.

His first season as head baseball coach was 1975, and he remained there until his retirement in 2000. Along the way, his teams rolled up over 200 wins and appeared in the state tournament five times. Two of those trips resulted in runner-up finishes the 1980 meeting with Huntington East, and in 1983 against Martinsburg.

And the list of star players Parham coached seems endless Chuck Tate, Andy "Bam Bam" Wakefield, Larry Maiolo, Mason Basham, Larry Hickman, Joe Joe Maiolo, Larry Pat Farley, Phil Culicerto, Tim Epling, Phil Lane, Ronnie Fama, John O'Dell.

There were many others, and many of themare members of the Woodrow Wilson Baseball Hall of Fame.

"I was fortunate I came across some good ball players," Parham said. "You don't like to toot your own horn, but like a fella said, we put Woodrow Wilson baseball on the map."

Another was Ronnie Scott, who went on to work for NASA in Florida before returning to Beckley in 2010. Sadly, he passed away in May at age 59.

"He wanted to see baseball dominant again like it was when he played," Parham said.

When Parham retired from baseball in 2000 he stayed on as a biology teacher for one more year it was the emphatic end of an era at the school. Not only did Parham retire, but Culicerto retired after the 1999 football season, and Barksdale left the bench just months before Parham to take a coaching job in Aiken, S.C.

"Indeed it was," said Parham, now 74. "I enjoyed working with Coach Culicerto (as an assistant football coach). He was a great football coach, and he was a baseball supporter. He had seven sons play baseball for me. Three of them played in the state tournament."

After his retirement, Parham's was a familiar face in the stands at Woodrow baseball games. But in 2009, his ability to be a spectator slowed down when it was discovered that he had cancer.

Parham was diagnosed with multiple myeloma, a blood cancer that develops in the plasma cells located in bone marrow. The cancer did eventually go into remission, but Parham was still getting checkups when something told him he needed to go to Johns Hopkins in Baltimore.

It was there that he was introduced to autologous stem cell transplant. It's a procedure that involves collecting the patient's stem cells and following it up with high doses of chemotherapy or a combination of chemo and radiation. The process kills cancer cells while also killing blood-producing cells left in the bone marrow.

The collected stem cells are later transplanted back into the patient, allowing the marrow to produce new blood cells.

"I met a very interesting and a caring doctor up there, Dr. (Ivan) Borrello. He told me (about the transplant)," Parham said. "As a matter of fact, they have been doing this since 1980. He asked, 'What do you think about a stem cell transplant?' And I said yeah. Anything to get rid of this cancer.

"At that time my cancer was in remission, so he couldn't do anything. He said we would have to wait until it comes back. He hoped it didn't come back, but if it does ..."

It did, and in February he had the procedure performed.

"It came back in 2016, and when you're over 70 they don't usually do these things," Parham said. "But he felt like I was in good shape, which I think well, I know I am. I went through it, successful, no problems whatsoever.

"After teaching biology, I thought I knew some things. Now I know I know some things."

Just like baseball.

Email: gfauber@register-herald.com and follow on Twitter @GaryFauber

Excerpt from:
Woodrow Wilson baseball field to be renamed for Tom Parham - Beckley Register-Herald

Bone Marrow Stem Cells Comments Off on Woodrow Wilson baseball field to be renamed for Tom Parham – Beckley Register-Herald | August 6th, 2017

What causes the body to age?

The Greek Philosopher Aristotle thought it was the hearta hot, dry organ at the seat of intelligence, motion and sensation.

Fast-forward a few centuries, and the brain has overthrown the heart as master of thought. But its control over bodily agingif anywas unclear. Because each organ has its own pool of stem cells to replenish aged tissue, scientists have long thought that the body has multiple aging clocks running concurrently.

As it turns out, thats not quite right.

This week, a study published in Nature threw a wrench into the classical theory of aging. In a technical tour-de-force, a team led by Dr. Dongsheng Cai from the Albert Einstein College of Medicine pinpointed a critical source of aging to a small group of stem cells within the hypothalamusan ancient brain region that controls bodily functions such as temperature and appetite.

Like fountains of youth, these stem cells release tiny fatty bubbles filled with mixtures of small biological molecules called microRNAs. With age, these cells die out, and the animals muscle, skin and brain function declines.

However, when the team transplanted these stem cells from young animals into a middle-aged one, they slowed aging. The recipient mice were smarter, more sociable and had better muscle function. Andget thisthey also lived 10 to 15 percent longer than mice transplanted with other cell types.

To Dr. David Sinclair, an aging expert at Harvard Medical School, the findings represent a breakthrough in aging research.

The brain controls aging, he says. I can see a day when we are implanted with stem cells or treated with stem cell RNAs that improve our health and extend our lives.

Its incredible to think that a tiny group of cells in one brain region could be the key to aging.

But to Cai, there are plenty of examples throughout evolution that support the theory. Experimentally changing a few of the 302 neurons in the nematode worm C. elegans is often sufficient for changing its lifespan, he says.

Of course, a mammalian brain is much more complicated than a simple worm. To narrow the problem down, Cai decided to zero in on the hypothalamus.

The hypothalamus has a classical function to regulate the whole bodys physiology, he says, so theres a natural logic for us to reason that the hypothalamus might be involved in aging, which was never studied before.

Even so, it was a high-risk bet. The hippocampusbecause of its importance in maintaining memory with ageis the most popular research target. And while the hypothalamus was previously somehow linked to aging, no one knew how.

Cais bet paid off. In a groundbreaking paper published in 2013, he found that a molecule called NF-kappaB increased in the hypothalamus as an animal grew older. Zap out NF-kappaB activity in mice, and they showed much fewer age-related symptoms as they grew older.

But heres the kicker: the effects werent limited to brain function. The animals also better preserved their muscle strength, skin thickness, bone and tendon integrity. In other words, by changing molecules in a single part of the brain, the team slowed down signs of aging in the peripheral body.

But to Cai, he had only solved part of the aging puzzle.

At the cellular level, a cornucopia of factors control aging. There is no the key to aging, no single molecule or pathway that dominates the process. Inflammation, which NF-kappaB regulates, is a big contributor. As is the length of telomeres, the protective end caps of DNA, and of course, stem cells.

Compared to other tissues in the body, stem cells in the brain are extremely rare. So imagine Cais excitement when, just a few years ago, he learned that the hypothalamus contains these nuggets of youth.

Now we can put the two threads together, and ask whether stem cells in the hypothalamus somehow regulate aging, he says.

In the first series of experiments, his team found that these stem cells, which line a V-shaped region of the hypothalamus, disappear as an animal ages.

To see whether declined stem cell function contributes to aging, rather as a result of old age, the researchers used two different types of toxins to wipe out 70 percent of stem cells while keeping mature neurons intact.

The results were striking. Over a period of four months, these mice aged much faster: their muscle endurance, coordination and treadmill performance tanked. Mentally, they had trouble navigating a water maze and showed less interest in socializing with other mice.

All of these physiological changes reflected an acceleration in aging, Cai and team concluded in their article.

And the consequences were dire: the animals died months earlier than similar transgenic animals without the toxin treatment.

If the decline in stem cell function is to blame for aging, then resupplying the aged brain with a fresh source of stem cells should be able to reinvigorate the animal.

To test this idea, the team isolated stem cells from the hippocampus of newborn mice, and tinkered with their genes so that they were more resilient to inflammation.

We know the aged hypothalamus has more inflammation and that hurts stem cells, so this step was necessary, explained the authors.

When transplanted into middle-aged mice, they showed better cognitive and muscular function four months later. Whats more, they lived, on average, 10 percent longer than mice transplanted with other cell types. For a human, that means extending an 85-year life expectancy into 93. Not too shabby.

But the best was yet to come. How can a few cells have such a remarkable effect on aging? In a series of follow-up experiments, the team found that the pool of biological molecules called microRNAs was to thank.

microRNAs are tiny molecules with gigantic influence. They come in various flavors, bearing rather unimaginative names like 106a-5p, 20a-5p and so on. But because they can act on multiple genes at the same time, they pack a big punch. A single type of microRNA can change the way a cell workswhether it activates certain signaling pathways or makes certain proteins, for example.

While most cells make microRNAs, Cai found that the hypothalamus stem cells have a unique, very strong ability to pack these molecules up into blobs of membrane and shoot them out like a bubble gun.

Once outside the cell, the microRNAs go on a fantastic voyage across the brain and body, where they tweak the biology of other tissues.

In fact, when the team injected purified little bubbles of microRNAs into middle-aged mice, they also saw broad rejuvenating effects.

Cai explains: we dont know if the microRNAs are pumped out to directly affect the rest of the body, or if they first act on different areas of the brain, and the brain goes on to regulate aging in the body.

Even so, the aging field is intrigued.

According to Dr. Leonard Guarente, an aging biologist at MIT, the study could lead to new ways to develop anti-aging therapies.

Whats more, its possible the intervention could stack with other known rejuvenating methods, such as metformin, young blood or molecules that clean out malfunctioning cells.

Its possible that stem-cell therapy could boost the hypothalamus ability to regulate aging. However, scientists still need to know how stem cells link with the hypothalamus other main role, that is, releasing hormones.

Of course, injecting cells into the brain isnt a practical treatment. The team is now working hard to identify which of the thousands of types of microRNAs control aging and what exactly they do.

Then the goal is to validate those candidate anti-aging microRNAs in primates, and eventually, humans.

Of course humans are more complex. However, if the mechanism is fundamental, you might expect to see effects when an intervention is based on it, says Cai.

Stock Media provided by digitalreflections / Pond5

See the original post:
Breakthrough Stem Cell Study Offers New Clues to Reversing Aging - Singularity Hub

Skin Stem Cells Comments Off on Breakthrough Stem Cell Study Offers New Clues to Reversing Aging – Singularity Hub | August 6th, 2017

Very few people have ever heard ofthe concept of artificial skin transplants.That will change in the near future, though. Artificial skin transplants may be the one thing we need most to treat type 2 diabetes. The skin grafts based on CRISPR gene editing couldyield some very powerful results. Their first tests involving mice werepositive, butensuring the technology works for humans in the same way will besomething else entirely.

Alot of people may not like the sound of artificial skin transplants. It sounds a lot scarier than it really is, however. There is actually nothing to fear about them. In fact, we have been using artificial skin implants for several decades now.Burn patients often recover thanks to these implants, for example. Artificial skin implants have proven to be an invaluable tool in the world of healthcare so far, and it seems thenumber of use cases may be expanded upon. However,they havenever been deployed to treat diabetesup untilnow.

Scientists have now successfully used these implants to treat diabetes in mice. That is a major development in medicine. The researchers edited stem cells from newborn mice to control the release of ahormone stimulating insulin production. Once the cells were turned into skin grafts, they were given to mice suffering from diabetes.

The mice were not born with diabetes. Instead, researchers fed them high-fat diets to causeobesity. Acruel method, perhaps, thoughit is not uncommon to see this sort of thingin the medical sector. Obesity is still one of the main risk factors causing type 2 diabetes in humans. People with a high insulin resistance are particularly prone to developing thecondition. Diabeteswas induced in these mice usingsome modifications to create viable test criteria.

Once the mice received the artificial skin implants, their insulin resistance levels started to reverse. Additionally, they gained around half the weight as those not given the grafts. Thissuggests that people cantreat diabetes usingthese implants, although theywill not do much for anyone suffering from type 1 diabetes. Thosewho do suffer from that condition may soon have access to a cheap and efficient solution created from stem cells. The goal is to turn these stem cells into human skin over time.

There may be other clinical applicationsinvolving artificial skin implants we have yet to discover. Ever since doctors started treating burn patients with this technique, the quest to find other use cases has been in full effect. Thanks torecent breakthroughsin this field, one can now grow artificial skin in a lab. However, given the lack of human test subjects, finding other use cases has been pretty difficult. This is where the mice come into the picture, even though the results involving human subjects mightdiffer greatly.

This is not a cure for diabetes, but it is an approach to help people maintain their glucose levels. For now, it only works withtype 2 diabetes causedby obesity, but it is still an important breakthrough regardless. The bigger question is what other types of diseases may be treated through artificial skin implants.

Original post:
Scientists Use Artificial Skin Implants to Treat Type 2 Diabetes The ... - The Merkle

Skin Stem Cells Comments Off on Scientists Use Artificial Skin Implants to Treat Type 2 Diabetes The … – The Merkle | August 6th, 2017

Genetically engineered skin cells grafted onto mice can treat the animals diabetes and obesity, according to new research published August 2, 2017 in Cell Stem Cell.

Researchers edited skin stem cells from newborn mice using CRISPR-based technology so that the cells secreted a peptide that regulates blood sugar. Transplanting the cells onto mice showed the grafts increased insulin secretion and reversed weight gain from a high-fat diet, as well as overturned insulin resistance. The result is a small step toward developing a safe and durable gene therapy to treat diabetes in humans.

Weve had this idea for a long time, so its exciting to see that, indeed, it can work to deliver therapeutics, coauthor Xiaoyang Wu, a stem cell biologist at the University of Chicago, tells GEN.

In the study, Wu and colleagues worked with skin because it is a large organ and easily accessible. The cells multiply quickly and are easily transplanted. And, transplanted cells can be removed, if needed. Skin is such a beautiful system, Wu says, noting that its features make it a perfect medium for testing gene therapies.

The team worked with the gene that produces glucagon-like peptide 1 (GLP-1), a hormone that stimulates the pancreas to secrete insulin. The additional insulin takes excessive glucose out of the bloodstream, which regulates complications from diabetes. The hormone can also decrease appetite. Using the genetic engineering tool CRISPR, the team inserted a mutation, adding an antibody fragment to the gene that would make the GLP-1 last longer in the blood and an additional modification to the targeting vector that would also attach an inducible promoter. This switch turns the gene on, as needed, to make more GLP-1. The switch would be triggered by the administration of the antibiotic doxycycline.

Wu and colleagues then inserted the altered gene into skin cells and grew the cells in a culture. Once the skin cells had grown into multiple layers, the team transplanted the patches onto mice with intact immune systems. Surprisingly, the mice didnt reject the graftsa feat in itselfsince human skin transplants are far more advanced than mice grafts, partly due to the animals furry skin.

Next, the team fed the mice small amounts of doxycycline. As a result, the animals released GLP-1 into the blood and had higher levels of insulin and lower levels of glucose. When fed a high-fat diet, the mice gained weight and became obese. But when the mice also were fed doxycycline so they secreted GLP-1, they gained less weight, showing the gene therapy was successful.

This kind of therapy could be potentially effective for many metabolic disorders, Wu says. The grafts could be used in patients who cant process protein or in individuals with hemophilia. The team is now testing the gene-therapy technique in combination with other medications.

See the article here:
CRISPR Gene Therapy via Skin Grafts Treats Obesity and Diabetes in Mice - Genetic Engineering & Biotechnology News

Skin Stem Cells Comments Off on CRISPR Gene Therapy via Skin Grafts Treats Obesity and Diabetes in Mice – Genetic Engineering & Biotechnology News | August 6th, 2017

The secret to healing what ails you lies within your own DNA.(photo credit:DREAMSTIME)

Scientists have, for the first time, corrected a disease-causing mutation in early-stage human embryos using gene editing.

The technique, which uses the CRISPR- Cas9 system, corrected the mutation for a heart condition at the earliest stage of embryonic development so that the defect would not be passed on to future generations.

It could pave the way for improved in vitro fertilization outcomes as well as eventual cures for some thousands of diseases caused by mutations in single genes.

The breakthrough and accomplishment by American and Korean scientists, was recently explained in the journal Nature. Its a collaboration between the Salk Institute, Oregon Health and Science University and South Koreas Institute for Basic Science.

Thanks to advances in stem cell technologies and gene editing, we are finally starting to address disease-causing mutations that impact potentially millions of people, said Prof. Juan Carlos Izpisua Belmonte of Salks gene expression lab and a corresponding author of the paper. Gene editing is still in its infancy, so even though this preliminary effort was found to be safe and effective, it is crucial that we continue to proceed with the utmost caution, paying the highest attention to ethical considerations.

Though gene-editing tools have the power to potentially cure a number of diseases, scientists have proceeded cautiously partly to avoid introducing unintended mutations into the germ line (cells that become eggs or sperm).

Izpisua Belmonte is uniquely qualified to speak on the ethics of genome editing because, as a member of the Committee on Human Gene Editing at the US National Academies of Sciences, Engineering and Medicine, he helped author the 2016 roadmap Human Genome Editing: Science, Ethics and Governance.

Hypertrophic cardiomyopathy is the most common cause of sudden death in otherwise healthy young athletes, and affects approximately one in 500 people. It is caused by a dominant mutation in the MYBPC3 gene, but often goes undetected until it is too late. Since people with a mutant copy of the MYBPC3 gene have a 50% chance of passing it on to their own children, being able to correct the mutation in embryos would prevent the disease not only in affected children but also in their descendants.

The researchers generated induced pluripotent stem cells from a skin biopsy donated by a male with Hypertrophic cardiomyopathy and developed a gene-editing strategy based on CRISPR-Cas9 that would specifically target the mutated copy of the MYBPC3 gene for repair. The targeted mutated MYBPC3 gene was cut by the Cas9 enzyme, allowing the donors cells own DNA -repair mechanisms to fix the mutation during the next round of cell division by using either a synthetic DNA sequence or the non-mutated copy of MYBPC3 gene as a template.

Using IVF techniques, the researchers injected the best-performing gene-editing components into healthy donor eggs that are newly fertilized with donors sperm. All the cells in the early embryos are then analyzed at single-cell resolution to see how effectively the mutation was repaired.

They were surprised by the safety and efficiency of the method. Not only were a high percentage of embryonic cells get fixed, but also gene correction didnt induce any detectable off-target mutations and genome instability major concerns for gene editing.

The researchers also developed an effective strategy to ensure the repair occurred consistently in all the cells of the embryo, as incomplete repairs can lead to some cells continuing to carry the mutation.

Even though the success rate in patient cells cultured in a dish was low, we saw that the gene correction seems to be very robust in embryos of which one copy of the MYBPC3 gene is mutated, said Jun Wu, a Salk staff scientist and one of the authors.

This was in part because, after CRISPR- Cas9 mediated enzymatic cutting of the mutated gene copy, the embryo initiated its own repairs. Instead of using the provided synthetic DNA template, the team surprisingly found that the embryo preferentially used the available healthy copy of the gene to repair the mutated part.

Our technology successfully repairs the disease-causing gene mutation by taking advantage of a DNA repair response unique to early embryos, said Wu.

The authors emphasized that although promising, these are very preliminary results and more research will need to be done to ensure no unintended effects occur.

Our results demonstrate the great potential of embryonic gene editing, but we must continue to realistically assess the risks as well as the benefits, they added.

Share on facebook

Read the rest here:
Early gene-editing holds promise for preventing inherited diseases - The Jerusalem Post

Skin Stem Cells Comments Off on Early gene-editing holds promise for preventing inherited diseases – The Jerusalem Post | August 6th, 2017

If you look at your skin, most of what you will see is actually dead cells. This thin outermost sheet protects the living cells underneath as they develop.

Thats why people exfoliatebecause your skin cells are designed to mature and slough off, says Thierry Work, a wildlife disease specialist with the U.S. Geological Survey. In June, he and his colleagues reported that they successfully mimicked this process with sea turtle skin. No, they didn't give sea turtles a facial, but they did grow layers of turtle skin in the lab.

Work is studying the virus responsible for a deadly disease called fibropapillomatosis, which causes tumors to grow all over sea turtles skin and inside their bodies. In order to grow this virus we have to basically replicate skin in the lab, because this virus will only grow when skin cells are maturing, he says. Cultivating the elusive virus may help researchers save sea turtles and perhaps shed light on how herpes viruses replicate in people.

Works efforts represent the first time that scientists have engineered reptile skin, but weve been building our own lab-grown versions of mammalian skin for decades. Lab-made skin can help us find treatments for diseases, heal wounds, spare animals from cosmetics testing, and design leather that emulates the look and feel of real animal hides. Heres how were imitating skin to benefit humans and other creatures.

Turtle trouble

Fibropapillomatosis most often strikes endangered green turtles, although it sometimes shows up in other species of sea turtles. The illness can debilitate turtles by growing tumors that prevent the animals from seeing properly or eating, and by suppressing the immune system.

To combat this disease, scientists must examine how the virus (Chelonid herpesvirus 5, or ChHV5 for short) multiplies in living cells. So Work and his team collected skin samples from green turtles with fibropapillomatosis that had just died or had to be euthanized. They then made a gel from collagenthe same protein that gives skin its firmnessand seeded it with cells taken from deep within the donated skin. Its this layer that we see when we examine a leather handbag or pair of shoes, Work says. Finally, his team grew surface skin cells on top of this scaffold.

The fruits of their labors are little plugs of skin only about 5 to 6 millimeters wide. But under the microscope, they look just like actual turtle skin, Work says.

Chelonid herpesvirus 5 and some other viruses (such as the one that causes warts in people) cant be grown in a lab without an environment that mimics the shape of skin and is populated by live, maturing cells.

Other viruses are less demanding, including herpes simplex (cause of cold sores and genital herpes in humans). Normally, herpes simplex and other viruses are grown on a flat lawn of skin cells in a petri dish. But this setting doesnt really recreate the shape and structure of real skin. So there may be insights were missing by cultivating viruses in a dish. We really havent seen what the virus does in the actual three-dimensional structure of reconstructed skin, Work says.

When he and his colleagues grew ChHV5 in their turtle skin, the pathogen did not behave as expected. The viruses formed odd looking, sun-shaped structures to serve as factories in the cells where the virus settled in and made copies of itself. The way all these components were being put togetherwas quite different than what people saw with conventional herpes viruses, Work says.

It could be that herpes simplex, and other herpes viruses that infect people, also form similar structures to assemble fresh recruits. The replication of the herpes virus is actually a lot more complicated than what people thought, Work speculates. The more we know about how viruses actually interact with cells, the more effective drugs we can design.

Now that scientists can cultivate ChHV5 in the lab, the next step is to come up with a blood test for fibropapillomatosis. That would tip them off that the disease is on the loose in a particular area before turtles begin to die. Theyre in a world of hurt, and by the time theyre heavily tumored its really too late to do anything, Work says.

It wont be practical to vaccinate or treat all the turtles directly. But we may be able to discourage the diseases transmission, the same way we use insecticides and bed nets to thwart mosquitoes from passing on malaria.

And now that reptile skin has been successfully grown in the lab, the technique could be put to work investigating other reptile and amphibian skin diseases. Engineered hide might help us learn more about snake fungal disease, which threatens snakes in the eastern and Midwestern United States, or the chytrid fungus that has infected frogs around the globe.

Healing wounds

Turtle skin doesnt have hair follicles or sweat glands, Work says. So its a bit easier to engineer than human skin. Nevertheless, the technique he used to emulate sea turtle pelts was adapted from ones commonly used to grow our own version of human skin.

Skin substitutes are an alternative to using grafts transplanted from elsewhere on a patients body to cover burns or other chronic wounds. Theres going to be a limited number of times that patients will allow the grafts to be taken from their thighs. These products that are ready-made became very popular because of that, says Vincent Falanga, an emeritus professor in the Boston University School of Medicines department of dermatology, whose studies on living bioengineered skin led to the U.S. Food and Drug Administration approving it to help non-healing wounds close more quickly.

Unlike skin grafts, bioengineered skin does not stick around, and eventually disintegrates. It does, however, protect the wound and stimulate the skins natural healing processes. Using bioengineered skin is a less painful process than undergoing skin grafts and may cause fewer complications, although its also more costly in general.

Bioengineered skin is often grown using cells taken from newborns foreskins. However, the vigorous young cells may stimulate the damaged area so much that it requires more energy than it can supply, Falanga says. Bioengineered skin that relies on less-active adult cells might actually be more effective in helping wounds to heal.

Skin substitutes dont quite function like the real thing. Last year, though, researchers in Japan reported that theyd grown realistic mouse skin from stem cells and successfully transplanted it onto other rodents. Previously when scientists grew skin from stem cells, they only managed to make sheets of cells emulating the skins outermost layer. But the new skin recreated all three of the layers found in skin, as well as boasting hair follicles and sebaceous glands (which make a fatty secretion to lubricate the skin).

Falanga is skeptical that this kind of engineered skin will perform well in chronic wounds. People in the bioengineering field, they want to reproduce whats already in nature, he says. We want to have a product that looks exactly like skin. Yet lingering wounds lack proper blood supply or have other problems that prevent them from healing. So they may be unable to maintain normally functioning skin, with its high energy demands.

However, the team in Japan hopes their lab-grown skin will eventually help people with burns, scars, or skin diseases like alopecia. "Up until now, artificial skin development has been hampered by the fact that the skin lackedimportant organs, such as hair follicles and exocrine glands, coauthor Takashi Tsuji, of the RIKEN Center for Developmental Biology, said in a press release. With this new technique, we have successfully grown skin that replicates the function of normal tissue.

The realistic skin also brings scientists closer to their dream of growing whole organs that can be transplanted into people, Tsuji said.

Sparing animals

But medical treatments aren't the only uses for skin substitutes. Tsuji and his team also have another goal in mind for their creation: Eventually, the realistic skin could be used for testing out cosmetics in lieu of animals.

There are already several companies devoted to just this purpose. Boston-based MatTek sells their lab-grown skin to other companies that make laundry detergent, makeup, anti-aging creams, and other chemicals.

Like Works sea turtle skin, these nubbins of skin are tinyjust a fraction of a millimeter thick. They are grown from skin cells left over after surgical procedures like tummy tucks and circumcisions. This skin is a better proxy for actual human hide than animals are, one of MatTeks customers told Wired last year.

Lab-made skin will soon provide an alternative to leather, too. Brooklyn-based startup Modern Meadow genetically engineers animal cells to produce collagen, which they use to make leather that resembles actual animal pelts. The biofabricated leather takes two weeks to grow, as opposed to the years it takes to raise an animal, slaughter it, and tan its hide. And because the cell-spun leather lacks features like hair and fat, its more eco-friendly to treat than the real thing.

Could Works lab-grown reptile hide also be used instead of skin from actual snakes or alligators for bags and shoes? Youd need to optimize this technique quite a bit before you got to that scale, he says. But I certainly think its possible.

Also apparently on the table: using DNA from a deceased fashion icon to grow skin for leather jackets and bags. Designer Tina Gorjanc wants to create artificial skin using Alexander McQueens genetic material, harvested from hair he used in a 1992 collection. Shes filed a patent in the United Kingdom for the process, although for now her prototypes are made from pig leather treated to look like human skin.

Read more from the original source:
Growing skin in a lab has benefits for humans and turtles alike - Popular Science

Skin Stem Cells Comments Off on Growing skin in a lab has benefits for humans and turtles alike – Popular Science | August 5th, 2017

Most nights, Marcia Dunlap attaches seven or eight leeches around her husband John's eyes as part of an effort to restore some of his vision. Tom Bailey/The Commercial Appeal

With the help of his wife Marcia, John Dunlap receives his nightly leech treatment at his home in East Memphis. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

At home most evenings, Memphis, Tennessee, attorney John Dunlap, 80, unbuttons and removes his white dress shirt and counting his steps and remembering which way to turn carefullywalks with a tall white canefrom the living room to the dining table, where his wife Marcia has a plastic container of leeches.

Twenty-six months ago,the couple's schizophrenic sonAndrewattacked them in theirhome. The injuries blinded Dunlap. He's in total darkness.

After drapinga large, peach-colored towel around John's neck, Marcia reaches into the water for the skinniest leeches. Those are the hungriest and most likely to latchonto John's face.

One at a time, she gently presses four leeches to the skin around John's left eye and three around the right. She waits patiently wait for eachto bite and stay connected to John's skin.

"You can feel a bite,'' he says. "A little, stinging bite... And then after awhile you don't feel anything.''

The Dunlaps have carried out this unusualroutine60 or so times since December. It's a type of therapy prescribed by a Los Angeles doctor who offers experimental stem cell therapy designed to regenerate tissue.

"In the beginning he made it very clear he's not anophthalmologist and not an eye surgeon but he had had some success with stem cells in treating blindness. It's experimental,'' Dunlap said.

Autoplay

Show Thumbnails

Show Captions

The doctor prescribed the leech therapy as a preliminary step because, Dunlap said, the leech enzymesenhance the blood supply to the eye and nourishthe eye tissue.

The left eye had atrophied, or withered. The idea wasto restore health to the eyebefore the stem cell treatment. There is no right eye, but the hope is that the leech enzymes will help revive that optic nerve in case a transplant is ever possible.

Since the leech therapy,the pressure in the right eye has improved significantly, Dunlapsaid, referring to follow-upexams. The retina, which had folded into an ice-cream cone shape after the trauma, has begun returning to its normal shape, he said.

Even though he still cannot see out of the left eye and the optic nerve remains severed from the retina, Dunlap said, "I now have a live eye.''

The Dunlaps decline to identify the California doctor, describing him as a"humble'' person whodoes not seek the publicity.

With the help of his wife Marcia, John Dunlap receives his nightly leech treatment at his home in East Memphis. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

Andrew, the Dunlaps' mentally ill son, is charged with attempted murder and domestic assault, and remains in jail awaiting trial. Thecouplehave told authorities that they mainly want Andrew to receive mental health treatment.

The Dunlapshave experienced tragedy long before the 2015 assault.

Their son Jeff, one of four children, was a St. Jude Children's Research Hospital patient who died of cancer at age 10, in September 1974.

Dunlap recalls a return car tripfrom Knoxville, where he and Marcia had been visiting grandchildren shortly after he was released from rehab.

"As we were driving back I started thinking of all the things I won't get to do again. In my mind, I was going down the list,'' he said.

It would be a long list, including some leisure activities he loves. An avid Cubs fan, heenjoyed attending spring training games in Arizona. A passionate golfer, he enjoyedwatching how the ball flew when he struck it well.

But Dunlap stopped himself from completing the list of losses, telling himself, " 'You don't want to dwell on that'. . . It's as if the Lord sent me a message that hit me across my forehead, saying, 'John, get over it. It could be a whole lot worse.'

"Anytime I want to start thinking about the things I'm missing or not doing what I used to do, I think 'Get over it. Move on'.''

Sudden blindness is such a change in lifestyle. "I guess some people may feel the world has ended for them, but it hasn't,'' he said.

Marcia Dunlap gets special leeches for her husband John's nightly treatment from the laundry room where she keeps it out of sight. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

The stem cell and leech therapy is expensive and not covered by health insurance. Some have expressed their skepticism about the legitimacy of the experimental treatments.

"You have some people who are concerned for you, that your approach is not going to be effective,'' Dunlap said.

"Yet, several folks up herehave said, 'John, I'd take a shot at it. It is expensive but you're the one with the white cane and the one who is blind and has to live with it. You have everything to gain and nothing to lose.'''

While some might be concerned about the unusual treatments, many others are inspired by the Dunlaps,saidBlanche Tosh, a fellow church member and friend since high school.

"I have told them so many times, 'You just can't begin to know the lives you have affected,'' Tosh said.

"I know so many people who look at the way they are dealing with multiple things. How could anybody endure that and just go on and be pleasant and make it from day to day with the consistent attitude that the world sees.

"You are not going to find many people whoever see one of them without a smile,'' Tosh said.

She was inspired to start a gofundme account (gofundme.com/johndunlapvision) to help coverthe Dunlaps' expenses. As of midweek, $8,795 of the $100,000 goal had been raised.

Memphis lawyer John Dunlap and his wife Marcia continue to search for some medical procedure to restore at least partial vision after John was blinded a few years ago when their mentally ill son attacked him. (Photo: Jim Weber/The Commercial Appeal)

Since December, Dunlap has undergone two-and-a-half rounds of leech therapy and two series ofstem cell treatments. The couple traveled to California in June for the most recent stem cell procedures, and returned home with stem-cell eye drops and injections.

Nowthey are in the middle of the leech therapy they resumed this summer.

John has a follow-up exam next week, when he will learn if there's been continued progress from the stem cell and leech therapies.

The California doctor "indicated it would take two to three months to see if we were getting any results from stem cell therapy out there,'' Dunlap said. That time could come sometime this month or in September.

If the stem cell therapy has not worked by then, he said,"We'll just have to see what any third plan looks like, and the cost involved.''

Late in life, Dunlap has been forced to learn to type, work a computer, navigate with a cane, count the steps and memorize the turns from one spot to another, communicate with Siri, and smile as blood-sucking leeches dangle from his cheeks.

Asked about his sources of inner-strength, he responded, "I don't know I'd call it inner-strength.

"I can tell you I certainly believe in the Lord. We pray daily. I appreciate the prayers of others. I think it certainly is a faithissue.''

He also credits his late mother, Cora, a single parentwho managed a grocery. "She was a very optimistic, loving person,'' he recalled.

"And I've had Marcia's support. Marcia wasn't going to let me give up, just sit down and do nothing.''

The Dunlaps are starting to consider resuming their annual trips to Cubs spring training in Arizona. Maybe next spring.

"You may have your vision by then,'' Marcia told John.

"I might,'' he responded."We'll see.''

Read or Share this story: https://usat.ly/2wtjL7V

Read the original here:
Will putting leeches on his face help this blind man see? - USA TODAY

Skin Stem Cells Comments Off on Will putting leeches on his face help this blind man see? – USA TODAY | August 5th, 2017

BINGHAMTON (WBNG) -- Thursday, a cancer survivor met her bone marrow donor for the first time, just days before her wedding.

"They told me that without a transplant I really only had about six months to a year," said Vivian Nolan, a bone marrow transplant recipient.

In 2008, Vivian Nolan was diagnosed with a rare form of cancer called multiple myeloma. Later on, she was diagnosed with leukemia.

Doctors tried a bone marrow transplant with her own stem cells. When that didn't work, they said she needed a donor.

"The only cure or chance of holding it off at all is a bone marrow transplant," Nolan said.

Lucky for Nolan, doctors found a match.

A stranger volunteered to save her life. Scott Durbin is Nolan's donor. He lives in Kentucky, over 850 miles away.

Thursday, Durbin and Nolan met for the first time.

Nolan is getting married on Saturday.Durbin and his family flew in to support her in her next phase of life, a life that she wouldn't have without him.

"This is the man who gave me my life back. So I'm really happy," Nolan said.

For Durbin, the decision to help someone in need was second nature.

"I signed up. 7 months later I got that phone call saying they was gonna fly me to Atlanta," bone marrow donor Scott Durbinsaid.

Nolan was still in shock that someone would do something so kind for a person he had never met.

"I just couldn't believe that there was someone out there that I never knew that would go through that for me," she said.

After the transplant, Nolan wanted to meet the man who now is a part of her.

Today, she was able to introduce her family to its newest member.

"Now I've got this whole new life and he's got this whole big new family."

For Durbin, it's a choice he'd make over and over.

"I would do it again to give you a second chance," Durbin said.

Nolan remains forever grateful for that second chance.

Since her bone marrow transplant, Nolan's leukemia is virtually gone. She says she feels great, and can't wait for her new lease on life.

Read the original here:
Cancer survivor meets bone marrow donor days before wedding - WBNG-TV

Bone Marrow Stem Cells Comments Off on Cancer survivor meets bone marrow donor days before wedding – WBNG-TV | August 5th, 2017

In 2002, Ian Thompson, a specialist in facial reconstruction at Kings College, London, received an urgent phone call. A patient in his late 20s had been struck by an out-of-control car mounting the pavement. The impact had sent him catapulting over the bonnet of the car, smashing his face and shattering the fragile orbital floor the tiny bone, no more than 1mm thick, which holds the eyeball in place in the skull.

Without the orbital floor, your eye moves backwards into the skull, almost as a defensive mechanism, Thompson explains. But this results in blurred vision and lack of focus. This patient had also lost the ability to perceive colour. His job involved rewiring aircraft and as he could no longer detect a red wire from a blue one, hed barely been able to work in three years.

The accident had happened three years earlier. Since then, surgeons had desperately tried to reconstruct the bony floor and push the eye back into position, first using material implants and then bone from the patients own rib. Both attempts had failed. Each time, infection set in after a few months, causing extreme pain. And now the doctors were out of ideas.

You might also like: How ancient skeletons are helping modern medicine The viruses that may save your life I was blind now I have bionic eyes

Thompsons answer was to build the worlds first glass implant, moulded as a plate which slotted in under the patients eye into the collapsed orbital floor. The idea of using glass a naturally brittle material to repair something so delicate may seem counterintuitive.

But this was no ordinary glass.

If you placed a piece of window glass in the human body, it would be sealed off by scar tissue, basically wobble around in the body for a while and then get pushed out, says Julian Jones, an expert in bioglass at Imperial College London. When you put bioglass in the body, it starts to dissolve and releases ions which kind of talk to the immune system and tell the cells what to do. This means the body doesnt recognise it as foreign, and so it bonds to bone and soft tissue, creating a good feel and stimulating the production of new bone.

Bioglass actually works even better than the patients own bone Ian Thompson

For Thompson, the results were immediate. Almost instantaneously, the patient regained full vision, colour and depth perception. Fifteen years on, he remains in full health.

Thompson has gone on to use bioglass plates to successfully treat more than 100 patients involved in car or motorcycle accidents. Bioglass actually works even better than the patients own bone, Thompson says. This is because weve found that it slowly leaches sodium ions as it dissolves, killing off bacteria in the local environment. So, quite by chance, you have this mild antibiotic effect which eliminates infections.

Cutting edge

Bioglass was invented by US scientist Larry Hench in 1969. Hench was inspired by a chance conversation on a bus with an army colonel who recently had returned from the Vietnam War. The colonel told Hench that while modern medical technology could save lives on the battlefield, it could not save limbs. Hench decided to shelve his research into intercontinental ballistic missiles and instead work on designing a bionic material which would not be rejected by the human body.

Hench ultimately took his research to London, and it has been in Britain where some of the most revolutionary bioglass innovations are being made in fields from orthopaedic surgery to dentistry.

Over the last 10 years, surgeons have used bioglass in a powdered form, which looks and feels like a gritty putty, to repair bone defects arising from small fractures. Since 2010, this same bioglass putty has hit the high street as the key component in Sensodynes Repair and Protect toothpaste, the biggest global use of any bioactive material. During the brushing process, the bioglass dissolves and releases calcium phosphate ions which bond to tooth mineral. Over time, they slowly stimulate regrowth.

But many scientists feel that the current applications of bioglass are barely scratching the surface of what could be possible. New clinical products are being developed which could revolutionise bone and joint surgery like never before.

Sitting in his office in Imperial Colleges Department of Materials, Jones is holding a small, cube-shaped object hes dubbed bouncy bioglass. Its similar to the current bioglass but with a slight twist: subtle alterations in the chemical composition mean its no longer brittle. Instead it bounces,like a kids power ball as Jones describes it, and its incredibly flexible.

The point of this is that it can be inserted into a badly broken leg and can support both the patients weight and allow them to walk on it without crutches, without requiring any additional metal pins or implants for support. At the same time, the bouncy bioglass also will stimulate and guide bone regrowth while slowly, naturally assimilating into the body.

To regenerate large pieces of bone, for example in a really big fracture, its very important to be able to put weight on your leg, Jones says. And its really important that the bio-implant in your leg is able to transmit the force from your weight to the bone cells, like a signal. Our body makes its own bone in the architecture that its in, because the cells feel the mechanical environment. So to grow back a big piece of bone you need to be able to transmit the right signals to them. The reason why astronauts in space lose bone mass is because without gravity, the cells arent receiving the same information as they do on Earth.

Further alterations to the chemical makeup of bioglass produce a different form which is much softer and has an almost rubbery feel. It feels almost like a piece of squid at a seafood restaurant. This bioglass is designed for possibly the holy grail of orthopaedic surgery: cartilage repair.

Right now, surgeons attempt to repair damaged cartilage in arthritic hips or damaged knee joints with a fiddly procedure called microfracture. This involves smoothing over the damaged area to expose the bone underneath, then pricking it to release stem cells from the bone marrow which stimulate repair. But this results in scar cartilage and within a few years, as many athletes have found, the original problem returns.

As a solution, Jones is looking to produce bioglass which can be 3D-printed and then slotted into any hole in the cartilage. For the cells to accept it, the material must retain all the natural properties of cartilage. To test its effectiveness, Jones uses a simulator that has human knee joints from cadavers donated for medical research.

We simulate the walking action, bending, all the things a knee would do, and make sure that the bioglass actually preserves the rest of the joint and behaves as it should do, he says. If that works then well proceed to animal and then clinical trials.

This same bioglass could find an additional use in aiding people with chronic back pain due to herniated discs. At the moment surgeons treat this by replacing the dysfunctional disc with a bone graft which fuses the vertebrae in the back together. But while this takes away the pain, it results in a considerable loss in mobility. Instead, a bioglass implant could be printed and simply inserted to replace the faulty disc.

It seems the obvious thing to do, Jones says. So far nobody has been able to replicate the mechanical properties of cartilage synthetically. But with bioglass, we think we can do it.

Weve just got to prove that we can. If all goes well and we pass all the necessary safety tests, it could reach the clinic in 10 years.

Using man-made materials which can fuse to the body may seem far-fetched but it is appearing to be a more and more likely component of future medicine. Already, millions of people brush their teeth with it. And that may just be the start.

This story is a part of BBC Britain a series focused on exploring this extraordinary island, one story at a time. Readers outside of the UK can see every BBC Britain story by heading to theBritain homepage; you also can see our latest stories by following us onFacebookandTwitter.

Join 800,000+ Future fans by liking us on Facebook, or follow us on Twitter.

If you liked this story,sign up for the weekly bbc.com features newsletter, called If You Only Read 6 Things This Week. A handpicked selection of stories from BBC Future, Earth, Culture, Capital and Travel, delivered to your inbox every Friday.

Read the original:
The best way to fix broken bones might be with glass - BBC News

Bone Marrow Stem Cells Comments Off on The best way to fix broken bones might be with glass – BBC News | August 5th, 2017

Affimed Therapeutics (NASDAQ:AFMD)

Q2 2017 Earnings Conference Call

August 1, 2017 8:30 AM ET

Executives

Anca Alexandru Head of Communications

Adi Hoess Chief Executive Officer

Florian Fischer Chief Financial Officer

Analysts

Maury Raycroft Jefferies

Do Kim BMO Capital Markets

Michael Schmidt Leerink

Peter Lawson SunTrust

Operator

Good day and welcome to the Affimed Second Quarter 2017 Financial Results and Corporate Update Conference Call. Todays conference is being recorded. At this time, I would like to turn the conference over to Anca Alexandru. Please go ahead.

Anca Alexandru

Thanks. I would like to welcome you to our investor and analyst call on the results for the second quarter of 2017. On the call with me today are Adi Hoess, CEO of Affimed, who will present the corporate update; and Florian Fischer, Affimeds CFO, who will walk you through the financials.

Slide 2, before we start, please note that this call and the Q&A session contains forward-looking statements, including statements regarding our future financial condition, business strategy, and our plans and objectives for our future operations.

These statements represent our beliefs and assumptions only as of the date of this discussion. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

These forward-looking statements are subject to risks and uncertainties and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors including, but not limited to those identified under the section entitled risk Factors in our filings with the SEC and those identified under the section entitled cautionary statements regarding forward-looking statements in our Form 6-K filed with the SEC earlier today.

Thank you for your understanding. I will now hand the call over to our CEO, Adi Hoess, who will provide the corporate update.

Adi Hoess

Thanks a lot, Anca. Affimed has developed an immune cell engager and our clinical and preclinical pipeline based on tetravalent bi and trispecificantibody formats. Were an industry leader in NK cell engagement and our lead product candidate AFM13 is to our knowledge, the most advanced NK-cell engager in clinical development.

We also have a well-differentiated T-cell based approach, which includes our clinical candidate AFM11 and well provide an update on these clinical programs as well as our pre-clinical programs today. We employ about 75 full time equivalents with our headquarter located in Heidelberg, Germany, and affiliate offices in the U.S., that is Affimed Inc., as well as our subsidiary AbCheck in Plze, in the Czech Republic.

Slide 4. We have an unencumbered clinical and pre-clinical pipeline of NK and T-cell engagers, with our NK-cell engagers being developed in hematological diseases and solid tumors. Based on our NK-cell platform, we have one clinical and two pre-clinical programs in developments. And based on our T-cell platform, we have one program in our own clinical development. And second T-cell engager program based on our platform called AMV564 is being developed by Amphivena, a company of which we own about 18.5% fully diluted. AMV564 has recently entered clinical development.

Slide 5 summarizes our second quarter updates for our NK cell engager program. For AFM13, we have completed the dose escalation part of our Phase 1b combination study with Mercks Keytruda in Hodgkin Lymphoma and initiated the expansion phase. The AFM13 Phase 2a monotherapy trial in Hodgkin Lymphoma sponsored by the German Hodgkin Study Group is open to recruit under new study design, which includes patients pre-treated with both brentuximab vedotin and anti-PD1.

Columbia University has recently initiated a translational study of AFM13 in CD30-positive lymphoma with cutaneous manifestation and I will provide more detail later. We made further progress in our collaboration with MD Anderson Cancer Center to evaluate AFM13 in combination with MD Andersons NK cell product. In June, we presented new data for our NK cell engagers AFM24 and AFM26 at two conferences and I will go into detail later on this.

Slide 6 summarizes the progress, we have made with our T-cell engager. Two Phase 1 dose-escalation studies are ongoing with AFM11, which offer a significant opportunity to address the high unmet medical need in diffuse large B-Cell lymphoma and mantle cell lymphoma. We believe that both the properties of AFM11 and the design of our studies can attract, specifically, mutations of other drugs in development.

Both dose escalation studies, which are conducted in ALL and in NHL respectively are designed with accelerated titration followed by a classical 3+3 design. In both studies, AFM11 was overall well tolerated with no dose limits and toxicity observed to date. In the AFM11 study in relapsed refractory ALL, which was initiated in September 2016, patients are currently being recruited into the fourth dose cohort. 12 sites are open and recruiting in the Czech Republic, Poland, Russia, Austria and Israel.

As mentioned, no DLTs were observed in particular no AFM11 related grade 3 or grade 4 neurotoxicity or side effects are frequently observed with T-cell engaging antibody agents observed. In our study of AFM11 in relapsed refractory NHL, patients are currently being recruited into the third dose cohort. Recall that this study has been amended in the past to enroll patients under a new revised study design.

We believe that we have addressed this lower than effective recruitment by opening further trial sites. A total of 10 sites are now opened in the Czech Republic, Poland, Germany as well as the U.S. Like in our ALL trial, no AFM11 related grade 3 or grade 4 neurotoxicity was observed to date under their revised study design. We intend to provide regular update on both the AFM11 studies in the future.

A second T-cell engager program based on our platform is AMV564, a bispecific tetravalent CD33/CD3 antibody developed by Amphivena in AML. A Phase 1 study is recruiting. However, no further updates have been provided by Amphivena.

Slide 7 shows our platform, which is very distinguished from others as, in contrast, the most comparatives were developing tetravalent bispecific molecules. The bivalent binding of two receptors on two different cells enables high-affinity binding through the avidity effect, which is advantageous to maintain high specificity at very high affinity.

We believe that this is very important in order to obtain a favorable safety profile. Furthermore, our platform allows multi-specificity in the tailored PK. Further differentiating Affimed, while most immune cell engaging approaches to date focus on T cells, our technology platform reliably generates both T and NK-cell engagers.

While increasingly NK-cells are becoming a cornerstone of cancer immunotherapy, and we're excited to be pioneering this development. There are a number of reasons why NK-cell-based approaches are very attractive and one of the reasons is that there seems to be a positive correlation between NK-cell infiltration and clinical outcome in patients.

In this context, it has been described that a low cytotoxicity is associated with higher incidence of cancer. In addition, recent clinical data show improved anti-tumor responses of ex vivo expanded and activated NK-cell populations. NK-cell-based immunotherapy has recently advanced with different treatment approaches, including engagers, check points, cytokines and adoptive cellular transfer.

To-date, it seems that NK-cell-based approaches have this strong advantage of controlling a well manageable favorable safety profile. This creates an opportunity for NK-cell redirection to address the lack of recognition of cancer cells and also allows for potential combination of NK-cells with other approaches to enhance efficacy.

A common theme in all different cancer types is the ability of the tumor cell to evade recognition by the immune system and, specifically, by NK-cells as shown on Slide 9. Normally, NK-cells are capable of killing foreign or aberrant cells, like tumor cells, have acquired mechanisms to escape the so-called immune surveillance.

As a result, such NK-cells cannot recognize tumor cells as foreign or aberrant and, therefore, cannot fight them. We believe that our platform has the potential to overcome these limitations by disabling the tumor evasion mechanisms, and I will explain on the next slide what this belief is based on.

Our expertise and leadership in natural-killer cell-based approaches is one of our key assets. As we can see here, there are a multitude of activating and inhibitory NK-cell receptors being discovered that CD16A, a dominant activating receptor on innate immune cells, is the only activating receptor that triggers the cytotoxic activity of nave human NK cells, even in the absence of costimulatory signals.

Based on these properties and on our preclinical and clinical data generated to date, we believe that targeting CD16A is key for efficient recruitment of and killing by NK cells and macrophages. We have secured a solid IP position around CD16A targets.

Slide 10. We believe that through targeting CD16A with high affinity and specificity, the significant limitations of IgGs can differ. With our tetravalent bispecific immune cell engagers, we can restore NK-cell killing in tumor immune control, and this is depicted here.

Let me explain in more detail why we believe that our approach is superior compared to IgG-based approaches. The human body is not using NK-cell engagement by IgG to eliminate cancer cells. However, this mechanism is used for cells infected by viruses or bacteria.

In this situation, the human immune system generates a collagen antibody response that highly decorates such infected cells or organisms.

Highly decorated means that many different proteins are expressed on the cell surface, which can then be found bound by antibodies. This polyclonal and high-density binding leads to NK-cells killing upon high avidity XP binding, plus antibodies for CD16A on the NK-cell and other XP gamma receptors, for example, CD32 and CD64.

In the setting of targetable cancer cells, however, with IgG, the situation is very different. Firstly, the therapeutic molecule targets a single epitope. Hence, it confers ammonia killing response. And secondly, there are cancer cells which express only very low numbers of the desired target.

The consequence of this very low target density is an insufficient amount of IgG, decorating the cancer cells and thereby not being able to efficiently recruit immune cells. This is shown in the middle picture. Interesting, most therapeutic monoclonal antibodies are target-modulating antibodies, such as cetuximab, polatuzumab, gevokizumab, just to mention a few of them.

We are addressing this limitation by targeting CD16A with high affinity and specificity, as shown. Indeed, our immune cell engagers has the potential to elicit a robust NK-cell killing and immune control due to multivalent and apparent high-affinity binding to CD16A even at limiting antigen densities on the target.

Slide 11, furthermore, CD16A in confers additional superior engager features. The binding of immune cells through CD16A with high affinity and specificity induces NK-cell activation, which triggers an integrated immune response that can be mediated by both innate and adaptive immune cells. In particular, our NK-cell engagers do not bind to CD16B and neutrophils, which avoids the sync effect. Their affinity has been demonstrated to be over 1,000 fold higher than that of monoclonal antibodies and our engagers bind independently of the 158 valine phenylalanine polymorphism.

Most importantly, theres virtually no competition with plasma IgG, which is shown here. In the ground stage, CD16A on innate immune cells is occupied by polyclonal plasma IgG. But there is a huge excess of plasma IgG versus therapeutic antibodies, this creates a significant threshold for FC-based therapeutic antibodies, however, not for CD16A target enhancement.

Our tetravalent and bispecific molecules, which recognize a different epitope from CD16A, are virtually unaffected by plasma IgG. All these unique features result in overall increased potency and efficacy of NK-cell engagers.

Slide 12. Our lead candidate, CD30/CD16A-specific NK-cell engager, AFM13 is a first-in-class antibody suitable for mono and combination therapy. This has demonstrated safety and clinical activity in heavily pretreated Hodgkin lymphoma patients in a Phase 1 study. In this Phase 1 study, tumor shrinkage and potential responses were observed in patients treated with four weekly doses of at least 1.5 mg/kg of AFM13. In 62% of patients, which was eight out of thirteen patients, we observed tumor shrinkage in 23% of patients, which was a total of three out of thirteen experienced partial response. None of the patients experiencing a PR had been previously treated with brentuximab vedotin.

Recall, that in our investigation the Phase 2a trial for AFM13 in relapsed and refractory Hodgkin lymphoma, which is led by the German Hodgkin Study Group, we have previously guided to change the study protocol to ensure a recruitment of a homogeneous patient population pre-treated with both BV and anti-PD1 antibodies. The study is now open to recruit under the new study design.

We had also provided some preliminary data from patients enrolled under the original study protocol, where partial responses were observed in two of seven evaluated patients who had been pre-treated with brentuximab vedotin, but were anti-PD1 naive. This suggests, now, for the first time that AFM13 is active as a single agent in this heavily pre-treated group of patients and, in particular, that AFM13 is active post brentuximab vedotin. We have learned from the study sponsor that both after-responders had failed BV as the most recent treatment prior to AFM13 therapy, with one patient experiencing stable disease and the other one partial in the progressive disease under the BV treatment.

As previously guided, full data from the ongoing study will be presented upon its anticipated completion in 2019. And prior to that, a decision of data publication time points will be made together with the German Hodgkin Study Group.

We are further developing AFM13 as a combination therapy. Preclinical affinity has been demonstrated in combination with anti-PD1 in vivo in a PDX model. This has been the basis of our Phase 1b trial in relapsed refractory Hodgkin lymphoma in combination with Mercks Keytruda. And here, we have completed the dose escalation part of the trial. In detail, three patients were enrolled into dose levels one and two, respectively, and six patients were enrolled into dose level three. While no grade three or four adverse events related to the study treatment were observed, one DLT was observed in cohort 3, which was a repeated grade two infusion-related reaction, leading to discontinuation of AFM13 treatment. This event is classified as a DLT according to the protocol definition. No further DLTs occurred.

The dose expansion cohort has been initiated with the highest dose explored during dose escalation. Data readout is ongoing in the treated cohort and we intend to present data from the dose escalation at a scientific medical conference in the second half of 2017.

Another update this quarter is that Columbia University has initiated a translational Phase 1b/2a study to evaluate the validity of activity of AFM13 in patients with relapsed and refractory CD30-positive lymphoma with cutaneous manifestation. Affirmed is supporting this trial which is designed to allow for serial biopsies, thereby enabling assessment of NK-cell biology and tumor cell killing within the tumor environment. The first patient was enrolled into the study in July 2017. In general, we view CD30-positive lymphoma as an attractive indication that may broaden the potential of AFM13. In terms of further guidance, we will work together with Columbia University to provide update on this study.

Slide 13. Additional opportunities for our NK-cell engagers include combinations with adoptive NK-cell transfer. Patients on NK cells can be stimulated by monotherapy using NK-cell engagers to overcome tumor immune evasion and immunosuppression. Ex vivo expansion and stimulation of autologous NK-cells followed by reinfusion alone or in combination with NK cell engager, is a viable therapeutic approach providing increased numbers of activated NK cells. Alternatively, NK cells can be derived from peripheral blood, cord blood or IPS cells from healthy donors, which is an allogeneic setting, or from immortalized cells. After ex vivo stimulation and expansion, the NK cells are infused into the patients in combination with NK cell engagers.

We are investigating this approach with our partner MD Anderson. Initially, we plan to investigate AFM13 with MDACCs NK-cell product in the transplant setting. Preclinical research activities are on track and these are intended to be followed by Phase 1 clinical trial. Proof-of-concept for this combination would also pave the way for combinations of other pipeline product such as for AFM23.

Affimed holds an option to exclusive worldwide rights to develop and commercialize any product developed under the collaboration. In addition to our clinical product candidates, we have created a strong preclinical pipeline. Over the last quarter we have further characterized our most advanced preclinical candidates, AFM24 and AFM26, which we are developing for three solid tumors and multiple myeloma respectively.

Despite several marketed agents such as cetuximab and tyrosine kinase inhibitor or TKIs, there is a significant medical need for a novel approach to treat EGF receptor-positive tumor. Both efficacy and toxicity can be addressed. EGFR-blocking drugs have been described to have side-effects including serious skin toxicity which might impact physicians willingness to prescribe a drug. In terms of efficacy, there is a need to overcome intrinsic or acquired resistance. For example, there is no clear indication of efficacy of EGFR-blocking antibodies in patients with RAS mutation.

We are developing a first-in-class NK cell engager designed to overcome the limitations of conventional therapy. AFM24 is designed to effectively treat EGFR-expressing solid tumors, such as lung and neck, or colon cancers. It is an EGFR/CD16A targeting tetravalent bispecific antibody that is well differentiated from cetuximab, it is more potent cytotoxicity in vitro and in vivo including a potential to kill RAS-mutant cell lines. There is novel mechanism of action in safety profile and it has the potential to overcome intrinsic or acquired resistance, which is described by many patients with EGFR positive tumors.

AFM24s potent NK cell recruitment may enable the shift of the validated target EGF receptor, primary receptor block toward immuno-oncology. We have identified several development candidates for which we have initiated IND-enabling studies.

Slide 15, there are several factors which differentiate AFM24 from other therapy. Firstly, AFM24 is differentiated through its efficacy. Here you can see that in vitro, our NK cell engager which is highly potent tumor cell killing independent of RAS mutational status. In vivo, we have demonstrated efficacy in tumors resistant to EGFR targeting agents. Importantly, as shown in the graphs on the right hand side, AFM24 was similarly efficacious in a cetuximab-sensitive model.

Secondly, AFM24 is differentiated through safety, Slide 16. We have completed pilot toxicity studies in cynomolgus monkeys with no major safety findings. At the EACR-AACR-SIC Special Conference, we presented data on a dose-range binder study in which AFM24 was dosed up to 93.75 mg/kg and a repeated dose study in which AFM24 was dosed up to 30 mg/kg in 4 weeks.

No AFM24-related macro or microscopic changes were seen in tissues including vital organs, skin and injection site. Importantly, there was no evidence of skin toxicity in those studies. Also no signs of delayed toxicity was observed in the repeated dose study recovery animals. On a molecular level, we learned from in vitro toxicology studies but there was no cytokine release or NK cell proliferation in the absence of target cells. This further substantiates AFM24s potential beneficial safety profile.

Slide 17, like for EGFR targeted tumors, there is a significant need for a novel approach to treat multiple myeloma. Even though, new therapies have significant improved outcomes, cure still remains elusive and the medical need to achieve minimal residual disease negativity is not yet addressed.

MRD positivity is associated with a poorer prognosis, and it has been recorded that persistent MRD by predictive marker of unsustained complete response. A particular hurdle for therapeutics aimed at immune cell engagement are very high M-protein serum levels up to 170mg/mL. Indeed the competition by serum IgG is known to strongly impair antibody-dependent cell-mediated cytotoxicity, the activity of monoclonal antibodies.

We are developing AFM26 to overcome the limitations of conventional therapies in multiple myeloma. AFM26 is a first-in-class tetravalent bispecific antibody targeting BCMA/CD16A. Targeting BCMA and employing NK cell engagement offers the potential to achieve MRD-negativity. For AFM26, NK cell binding is largely unaffected by circulating IgG, which creates the potential of NK cell activation in the presence of M-protein.

Indeed, the high affinity binding to both target and NK cells leads to a prolonged cell retention. This is shown on the right on the slide on the right bottom. AFM26 shows high cytotoxicity cytotoxic activity towards both low and high BCMA-expressing myeloma cells. AFM26 may be potentially safer than T cell-based approaches, which would allow for faster development timelines. Based on these characteristics, AFM26 might be positioned in first line of combination with adoptive NK-cell transfer during ASCT or in a salvage setting.

AFM26 binds the B-cell maturation antigen, which is an antigen ubiquitously expressed on malignant plasma cells. Its expression on healthy tissues is limited to plasma cells and peripheral dendritic cells. We believe the BCMA is an ideal target for immunotherapy of multiple myeloma.

At ASCO and at the EACR-AACR-SIC, both in June, well present the data on AFM26 NK-cell binding properties and activity. As shown here, these data underscore that compared to native and FC-enhanced IgG. AFM26 shows improved binding and cell surface retention.

Slide 20, we also show that AFM26 is well differentiated through target cell binding in potent NK-cell mediated tumor cell lysis. And this is shown here in comparison with two marketed agents, daratumumab and anti-CD38 antibody and elotuzumab, which targets PS1. Importantly, other than described for daratumumab and elotuzumab, AFM26 did not induce NK-cell mutation.

Slide 21, like our other NK-cell engagers, AFM26 is also well differentiated for other agents [indiscernible] safety. Here you can see that compared to a T-cell engager, AFM26 is similarly potent that shows a reduced cytokine release pattern. This point is going to improve safety profile, making AFM26 uniquely suited to engage NK-cells with multiple myeloma.

I will now hand over the call to our CFO, Florian Fischer, who will provide further details on the financial figures.

Florian Fischer

Thank you, Adi. Affimeds consolidated financial statements have been prepared in accordance with IFRS as issued by the International Accounting Standards Board or IASB. The consolidated financial statements are presented in euro, which is the companys functional and presentation currency. Therefore, all financial numbers that I will present here in this call unless otherwise noted will be in euros. Any numbers referring to Q2 2017 and Q2 2016 are unaudited.

Cash and cash equivalents and financial assets totaled 48.9 million as of June 2017 compared to 44.9 million as of December 31, 2016. The increase was primarily attributable to the net proceeds of 16.4 million from a public offering of common shares in the first quarter, and of 2.5 million from the drawdown of the second tranche of the loan from Silicon Valley Bank, largely offset by operational expenses.

Net cash used in operating activities was 13.1 million for the six months ended June 30, 2017compared to 17 million for the six months ended June 30, 2016. The decrease was primarily related to lower cash expenditure for research and development in connection with Affimeds development and collaboration programs and to the expiration of the Amphivena collaboration.

Affimed expects to have cash to fund our operations at least until the end of 2018. This provides runway for the planned development of our clinical programs, as well as for product discovery and early development activity.

Revenue for the second quarter of 2017 was 0.5 million compared to 2.1 million for the second quarter 2016. Revenue in the 2017 period was primarily derived from AbCheck services, while revenue in 2016 period predominantly to Affimeds collaboration with Amphivena.

R&D expenses for the second quarter of 2017 were 5.4 million compared to 8.6 million for the second quarter of 2016. The decrease was primarily related to lower expenses for AFM13 and our discovery and early stage development activities and the expiration of the Amphivena collaboration.

G&A expenses for the second quarter of 2017 were unchanged at 2.0 million compared to the second quarter of 2016. Net loss for the second quarter of 2017 was 7.9 million, or 0.18 per common share, compared to a net loss of 8 million or 0.24 per common share for the second quarter of 2016.

The decrease of operating expenses was offset by lower revenue. In addition, the result was affected by finance costs of 1.2 million in the second quarter of 2017, whereas finance income of 0.5 million was shown in the second quarter of 2016.

I will now turn the call back over to Adi for a summary of our two clinical programs and our pipeline. Adi?

Adi Hoess

Thanks a lot Florian. Our strategy is to maximize the value of our unencumbered clinical and preclinical pipeline of NK-cell and T-cell engagers, as well as from our platform. Were leveraging our lead product, AFM13, for CD30-positive lymphoma initially focusing on the Hodgkin Lymphoma salvage setting enabling a fast development path and allowing the establishment of a cost efficient marketing and sales structure.

In addition, we believe investigating AFM13, both as monotherapy and in combination with Keytruda, reduces its development. Overall, our preclinical and clinical strategy is designed from the scientific leadership of our NK-cell platform with CD16A as proprietary target. We are expanding the preclinical and clinical activities of our tetravalent and bispecific NK-cell engager platform in solid tumors with our preclinical candidate AFM24 and in hematologic diseases, where we intend to leverage additional opportunities for AFM13 and AFM26, for example, in combination with adoptive NK-cells. We also develop T-cell engagers and our lead T-cell engager, AFM11, is being investigated in two ongoing ALL and NHL trials. BMV564, a T-cell engager derived from our technology platform, is in clinical development through Amphivena to treat AML.

In addition, as mentioned earlier, moving beyond our standard format, we are developing different tetravalent bispecific antibody formats tailored to specific indications and patient populations. And as outlined in previous earnings calls, we have more projects ongoing at the discovery stage and preclinically, including molecules developed from our MHD type complex targeting platform.

Thank you very much for your interest. The call is now open for questions.

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] Our first question now comes from Maury Raycroft from Jefferies. Please go ahead.

Maury Raycroft

Good morning. Thanks for taking my questions. So I was wondering if you can mention what the AFM13 dose was that the DLT patient received in the combo trial? And then what youre going to use in the expansion cohort? And then is this dose higher, lower or in line with your predictions?

Adi Hoess

Hi, Maury, this is Adi. What we have done is we have used or given a PD-1 as its active dose and have dosed up AFM13 under the following strategy, under the following regime. We always are initially giving AFM13 three times per week for two weeks. Then, we give AFM13 once weekly for six weeks and, subsequently, we dose AFM13 every three weeks. The starting dose was 0.15 mg/kg and then switching to 0.5 mg/kg, the next one was 0.5 mg/kg going to 1.5 mg/kg, and the highest dose was 3 mg/kg going then to 7 mg/kg. So the three is always three times per week, and the seven is the weekly or every three weeks. We have seen 1 DLT in the highest dose. So at three times 3 mg/kg and once 7 mg/kg then have included an additional three patients and have not observed another DLT. So thats why we decided to go with the highest dose of 3 mg/kg three times per week subsequently given and then subsequently followed by 7 mg/kg.

Maury Raycroft

Got it, okay. And you also mentioned earlier about the two PRs generated with the monotherapy treatment? And I think you said there is a stable disease, but I missed some of the additional context, and I was just wondering if you can recap that for me?

Adi Hoess

Originally posted here:
Affimed Therapeutics' (AFMD) CEO Adi Hoess on Q2 2017 Results - Earnings Call Transcript - Seeking Alpha

IPS Cell Therapy Comments Off on Affimed Therapeutics’ (AFMD) CEO Adi Hoess on Q2 2017 Results – Earnings Call Transcript – Seeking Alpha | August 5th, 2017

THURSDAY, Aug. 3, 2017 (HealthDay News) -- Scientists have created genetically altered skin cells that may control type 2 diabetes in lab mice. And they believe the general concept could someday be used to treat various diseases.

Using a combination of stem cells and "gene editing," the researchers created patches of skin cells that were able to release a hormone called GLP1 in a controlled manner.

The hormone, which is normally produced in the digestive tract, spurs the production of insulin -- the body's key regulator of blood sugar levels.

The scientists found that transplanting the engineered skin patches onto diabetic lab mice helped regulate their blood sugar levels over four months.

Xiaoyang Wu, a stem cell biologist at the University of Chicago, led the "proof of concept" study. He said it raises the possibility that "therapeutic skin grafts" could be used to treat a range of diseases -- from hemophilia to drug dependence.

Wu's team focused on type 2 diabetes in these initial experiments because it's a common condition.

However, a researcher not involved in the study doubted the usefulness of the approach for diabetes specifically.

People with type 2 diabetes already manage the disease with diet, exercise and medications -- including ones that target GLP1, said Juan Dominguez-Bendala.

Using high-tech gene therapy to get the same result seems unlikely, said Dominguez-Bendala, an associate professor at the University of Miami's Diabetes Research Institute.

"I don't see something like this coming to the clinic for diabetes," he said.

But Dominguez-Bendala also pointed to what's "cool" about the experiments.

Wu's team used a recently developed technology called CRISPR (pronounced "crisper") to create the skin patches. The technique, heralded as a major breakthrough in genetic engineering, allows scientists to make precision "edits" in DNA -- such as clipping a particular defect or inserting a gene at a specific location.

Before CRISPR, scientists could not control where an inserted gene would be integrated into the genome. It might end up in a "bad" location, Dominguez-Bendala explained, where it could, for example, "awaken" a tumor-promoting gene.

Wu and colleauges used CRISPR to make specific edits in GLP1, including one that allowed the gene to be turned "on" or "off" as needed, by using the antibiotic doxycycline.

The modified gene was inserted into mouse stem cells, which were then cultured into skin grafts in the lab. Finally, those grafts were transplanted onto lab mice.

The researchers found that when the mice were fed food with tiny amounts of doxycycline, the transplanted skin released GLP1 into the bloodstream. In turn, the animals' insulin levels rose and their blood sugar dipped.

The engineered skin also seemed to protect the mice from the ravages of a high-fat diet. When the mice were fed a fat-laden diet, along with doxycycline, they gained less weight versus normal mice given the same diet. They also showed less resistance to the effects of insulin, and lower blood sugar levels.

According to Wu, the study lays the groundwork for more research into using skin cells as a way to deliver "therapeutic proteins."

For instance, he said, skin cells could be engineered to provide an essential protein that is missing because of a genetic defect. As an example, he cited hemophilia -- a genetic disorder in which people lack a protein that allows the blood to clot properly.

Skin cells could be an ideal way to deliver such therapies, Wu said.

For one, the safety of skin grafts in humans is well-established, he pointed out. Since the 1970s, doctors have known how to harvest skin stem cells from burn victims, then use those cells to create lab-grown skin tissue.

Because the skin is generated from a patient's own stem cells, that minimizes the issue of an immune system attack on the tissue.

Dominguez-Bendala agreed that using skin cells has advantages. For one, he noted, the skin graft can be easily removed if something goes awry.

But a lot of work remains before therapeutic skin grafts could become a reality for any human disease. And research in animals doesn't always pan out in humans.

A next step, Wu said, is to see whether the skin grafts maintain their effects in lab mice over a longer period. The researchers will also monitor the animals for any immune system reactions against the GLP1 protein itself.

The findings were published online Aug. 3 in Cell Stem Cell.

The U.S. National Institutes of Health has a primer on gene therapy.

Visit link:
Engineered Skin Cells Control Type 2 Diabetes in Mice: Study - Arizona Daily Star

Skin Stem Cells Comments Off on Engineered Skin Cells Control Type 2 Diabetes in Mice: Study – Arizona Daily Star | August 4th, 2017

File Photo

EL PASO, Texas - Three new retailers are setting up shop inside Cielo Vista Mall.

Simon Properties announced the opening of three new stores: ThinkGeek, Adore Cosmetics, and Ooh La La.

Opening mid-August, ThinkGeek offers a wide assortment of "nerd interest-inspired" items, gadgets, apparel, and unique licensed products from pop culture brands like STAR WARS, Star Trek, Game of Thrones, Marvel, Nintendo, Minecraft, and various others.

The 2,172 square-foot store will be on the upper level, next to JCPenney.

Meanwhile, Ooh La La will give customers a number of options when it comes to snack foods. Specializing in traditional Mexican snacks, gift baskets and custom gift wrapping, the store will open mid-August next to LIDS.

Adore Cosmetics offers organic skin care products mostly powered by stem cells from plants. The cosmetics company's products are designed to "help reverse the signs of aging and restore a youthful glow to the skin be harnessing the power of nature," according to the store's description.

Slated to open late August, the store is located between Vitamin World and LIDS.

Shawn Thomson, General Manager of Cielo Vista Mall, says they are constantly searching for ways to keep new and veteran visitors happy.

"We are continually looking for opportunities to enhance our visitor's experience with a unique mix of retail offerings," Thomson said."We believe these new offerings will speak to our current customer base, giving them new options, while simultaneously attracting new customers to Cielo Vista Mall."

Continued here:
ThinkGeek, Adore Cosmetics and Ohh La La coming to Cielo Vista Mall - KVIA El Paso

Skin Stem Cells Comments Off on ThinkGeek, Adore Cosmetics and Ohh La La coming to Cielo Vista Mall – KVIA El Paso | August 4th, 2017

FREMONT, Calif., Aug. 03, 2017 (GLOBE NEWSWIRE) -- Asterias Biotherapeutics, Inc. (NYSE MKT:AST), a biotechnology company pioneering the field of regenerative medicine, today announced that two additional clinical sites have opened to enroll subjects for the companys ongoing SCiStar Phase 1/2a clinical study of AST-OPC1 in complete cervical spinal cord injury (SCI). The additional clinical sites include: Thomas Jefferson University Hospital, in partnership with Magee Rehabilitation Hospital, in Philadelphia, PA; and UC San Diego Health in San Diego, CA. Asterias now has eight clinical sites throughout the country enrolling patients in the study.

We are excited about the clinical site openings at Thomas Jefferson University Hospital and UC San Diego Health, stated Dr. Edward Wirth III, Chief Medical Officer of Asterias Biotherapeutics. These sites provide additional geographical reach and previous experience with spinal cord injury trials to our SCiStar study. We have recently reported completion of enrollment in four out of five cohorts in our SCiStar study so we hope these institutions will also participate in a future, larger study of AST-OPC1.

Each of the two additional clinical sites is recognized in the treatment of SCI:

The two additional clinical sites join existing clinical sites for the SCiStar study at the Medical College of Wisconsin in Milwaukee, Shepherd Medical Center in Atlanta, University of Southern California (USC) jointly with Rancho Los Amigos National Rehabilitation Center in Los Angeles, Indiana University, Rush University Medical Center in Chicago and Santa Clara Valley Medical Center in San Jose jointly with Stanford University.

Asterias has completed enrollment and dosing in four of the five planned SCiStar study cohorts and enrolled twenty patients in the SCiStar study. Twenty-five patients have been administered AST-OPC1 after including patients from a previous Phase 1 safety trial and results-to-date continue to support the safety of AST-OPC1. In June 2017, Asterias reported 9 month data from the AIS-A 10 million cell cohort that showed improvements in arm, hand and finger function observed at 3-months and 6-months following administration of AST-OPC1 were confirmed and in some patients further increased at 9-months. The company intends to complete enrollment of the entire SCiStar study later this year, with multiple safety and efficacy readouts anticipated during the remainder of 2017 and 2018.

About the SCiStar Trial

The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 patients with subacute motor complete (AIS-A or AIS-B) cervical (C-4 to C-7) SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A patients have lost all motor and sensory function below their injury site, while AIS-B patients have lost all motor function but may have retained some minimal sensory function below their injury site. AST-OPC1 is being administered 21 to 42 days post-injury. Patients will be followed by neurological exams and imaging procedures to assess the safety and activity of the product.

Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which has provided $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1.

Additional information on the Phase 1/2a trial, including trial sites, can be found at http://www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com).

About AST-OPC1

AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells originally isolated in 1998, has been shown in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site.

In a previous Phase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million AST-OPC1 cells at the spinal cord injury site 7-14 days post-injury. Based on the results of this study, Asterias received clearance from FDA to progress testing of AST-OPC1 to patients with cervical spine injuries in the current SCiStar study, which represents the first targeted population for registration trials. Asterias has completed enrollment in the first four cohorts of this study. Results to date have continued to support the safety of AST-OPC1. Additionally, Asterias has recently reported results suggesting reduced cavitation and improved motor function in patients administered AST-OPC1 in the SCiStar trial.

About Asterias Biotherapeutics

Asterias Biotherapeutics, Inc. is a biotechnology company pioneering the field of regenerative medicine. The company's proprietary cell therapy programs are based on its pluripotent stem cell and immunotherapy platform technologies. Asterias is presently focused on advancing three clinical-stage programs which have the potential to address areas of very high unmet medical need in the fields of neurology and oncology. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) is undergoing continuing development by Asterias based on promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML), with current efforts focused on streamlining and modernizing the manufacturing process. AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy. The company's research partner, Cancer Research UK, plans to begin a Phase 1/2a clinical trial of AST-VAC2 in non-small cell lung cancer in 2017. Additional information about Asterias can be found at http://www.asteriasbiotherapeutics.com.

FORWARD-LOOKING STATEMENTS

Statements pertaining to future financial and/or operating and/or clinical research results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias' filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements.

Read more:
Asterias Biotherapeutics Opens Two Additional Clinical Sites for ... - GlobeNewswire (press release)

Spinal Cord Stem Cells Comments Off on Asterias Biotherapeutics Opens Two Additional Clinical Sites for … – GlobeNewswire (press release) | August 4th, 2017

Invivo Therapeutics (NASDAQ:NVIV) (OTCQB:NVIVD) has paused patient enrollment in the approval trial of its bioresorbable spinal implant, Neuro-Spinal Scaffold, after a third patient in the study died. The company states that all three deaths have been determined to be unrelated to the product or the implantation procedure, used in patients rendered paraplegic by a spinal cord injury, but the company's shares tanked 27%.

Unless Invivo can somehow shake off the product's worrisome reputation - to this end, it is talking with the FDA to see if enrollment criteria ought to be changed or the study altered in other ways - it will have to rely on its one remaining product, an injected spinal cord injury therapy based on neural stem cells. But this is still in animal trials, so Invivo really needs its Neuro-Spinal Scaffold to be vindicated.

This is the second disappointment for the company in its attempt to develop this project. Four years ago the FDA refused to let it file on data from a pilot study, setting the approval date back by some years (InVivo Therapeutics suffers from FDA's timidity on biologic grafts, August 29, 2013).

The Neuro-Spinal Scaffold is made of two polymers, polylactic-co-glycolic acid and poly-L-lysine. It is implanted at the site of a spinal cord injury to provide structural support and a matrix through which the patient's neural tissue can regrow, after which the graft breaks down over several weeks.

The Inspire trial is testing its safety and probable benefit for the treatment of complete spinal cord injury at the T2-T12 and L1 positions - from roughly shoulder level to just above the waist. The primary endpoint is improvement of one or more grades on the on the American Spinal Injury Association impairment scale (AIS) at six months after implantation. The study is slated to enrol 20 patients, according to Clinicaltrials.gov, and is intended to support a filing for US approval via the humanitarian device exemption (HDE) route.

The most recent patient to sign up to the Inspire study underwent implantation in late June but died suddenly at a healthcare facility following discharge from the hospital.

Invivo could hardly be blamed for pointing out that some of the patients in the Inspire trial had had positive outcomes. One had improved from a complete injury (grade A on the AIS) to having some restored sensory and motor function (grade C) one month after treatment. Another had regained sensory but not motor function (grade B) at six months.

One patient who had improved from a complete injury (grade A) to having sensory function (B) at two months reverted to complete injury at three months, but was deemed to have regained this motor function at the six-month point. The company says that of the 16 patients currently in follow-up seven have improved on the AIS, four of whom have recovered both sensory and motor function to reach grade C.

Five further patients had not improved at six months, and four had shown no improvement but had not yet reached this point.

With trial enrollment on hiatus Invivo will have to wait to find out whether these results might be sufficient to get the graft an HDE approval. The company now hopes to complete enrollment in the first half of next year, and to file its FDA approval application in the second half of 2018.

Use of the Neuro-Spinal Scaffold in complete and incomplete spinal cord injury, at cervical and thoracic levels, is forecast to bring Invivo revenues of $268m in 2022, according to EvaluateMedTech's consensus. By 2022 the sellside sees it outsold by Invivo's only other product, a biomaterial-based scaffold used to deliver neural stem cells to help reconnect the spinal cord by re-growing nerves.

But the scaffold is the more advanced product, and Invivo will be relying on revenues from this to fund clinical development of the stem cell therapy. The trial delay puts this in jeopardy, as the company's shareholders are well aware.

Editor's Note: This article covers one or more stocks trading at less than $1 per share and/or with less than a $100 million market cap. Please be aware of the risks associated with these stocks.

See the rest here:
Third Trial Death Endangers Invivo - Seeking Alpha

Spinal Cord Stem Cells Comments Off on Third Trial Death Endangers Invivo – Seeking Alpha | August 2nd, 2017

School of Public Health (SPH) student Jake Maxon (Burnsville, MN) became interested in policy while working among microscopes and petri dishes. After getting his neuroscience degree from Brown University, Maxon researched spinal cord injuries, which involved stem cell research.

Policy around stem cells brought a different kind of challenge to our research, and I wanted to know more about how policies are created and implemented, he says.

So Maxon enrolled in SPHs Public Health Administration and Policy program, where hes been able to work with many Twin Cities policy organizations, including as a grant reviewer for the Ryan White HIV/AIDS Program and as a policy intern for Hennepin County.

But he wanted to understand policy on a federal level. So he applied to the White House Internship Program. After a six-month selection and vetting process, he was assigned to work alongside the three-person team in the Office of National AIDS Policy, which works to create an integrated approach to the prevention, care, and treatment of HIV/AIDS.

Weve advanced medical care for HIV/AIDS patients, so many people in our country forget that HIV is still an epidemic and its still a public health crisis, says Maxon. More than 4,300 residents in Hennepin County alone are currently living with HIV/AIDS.

While in Washington, D.C., Maxon continued working on his degree and now, nearly finished, finds himself in a new role as coordinator for Hennepin Countys HIV Positively Hennepin strategybased off of the national strategy he helped implement at the White House.

The vision is to create a county where all residents living with HIV/AIDS have healthy, vibrant lives, where there is equitable access to HIV prevention and care, and where there are no new HIV infections.

View original post here:
A bold vision - UMN News

Spinal Cord Stem Cells Comments Off on A bold vision – UMN News | August 2nd, 2017

We lost an American icon Thursday with the death of actor and playwright Sam Shepard. He had ALS (amyotrophic lateral sclerosis), more commonly known in the U.S. as Lou Gehrigs disease. Its an invariably fatal neurological disease that robs individuals of their ability to move muscles, their ability to swallow, and eventually, their ability to breathe.

ALS often starts in a fairly nonspecific way, with weakness in a persons hand or foot. Although I never examined the late Mr. Shepard, even in public photos from 2016, the atrophy of his hand muscle was evidenta hallmark of the loss of muscle that occurs in ALS.

In about 90% of cases diagnosed by neurologists, ALS happens out of the blueits sporadic, and the cause isnt known. About 10% of the time, ALS is inherited through a defective gene; that is, a patient has a family member who also had the disease. We can readily diagnose inherited ALS with a relatively simple blood test.

Five years ago, we learned that even in some patients who have no family history of ALS, a defect in a gene known as C9orf72 underlies the disease. In some patients, the disease may be initially diagnosed incorrectly as a nerve problem in the hands or wrist (carpel tunnel syndrome), or a pinched nerve in the neck or back. But those conditions are commonly associated with painALS is not generally a painful disease.

The weakness typically progressesslowly over many years in some patients, or rapidly over a few months in othersprogressing from one hand to the other, from hand to foot, or foot to hand. Eventually it affects ones ability to chew, swallow, and breathe. The weakness of the breathing muscles is what makes ALS fatal. Unlike cancer, with its rare but real remissions, ALS is always fatal. Patients might choose to have a ventilator artificially breathe for them; that intervention delays death, but not the progressive weakening and paralysis of all muscles.

As treating physicians, we have a paucity of options to slow down the disease and have no real effective drug to halt its relentless progression or to recover functionno cure. ALS is not really one disease, but a combination of different genetic, even environmental, insults, that culminate in this horribly disabling and life-ending malady. Not unlike what we have learned about cancers, there may be many different causesgenetic, molecular, biochemicalthat underlie the disease. In cancers, sampling the actual diseased tissue, commonly through tissue biopsies, has provided a trove of clues about what underlies the basis of the different cancers and how to approach the different forms, sometimes quite successfully. But with ALS, we cannot readily take a chunk of someones brain or spinal cord, so we are often left guessing as to what may underlie the cause of the disease and how to best treat it. That antiquated approach may soon end.

Advances in the generation of stems cells from individual patients provide the most powerful way to generate their own brain cells. We are now able to take a small tube of blood or skin and turn those cells into stem cells (by a procedure that won the Noble prize several years ago), and then, by adding a few more chemicals and special genes, turn those cells into motor neuronsbrain and spinal cord cells that die in ALS.

This procedure, which in essence creates a biopsy of the brain/spinal cord of ALS patients, will allow us to achieve what has been so successful in cancerto truly understand the different kinds of ALS, to use our patients brain cells to discover their individual disease causes, and to develop a more individualized pathway for drug therapy. We aim to personalize ALS therapywhat we call Answer ALS. That is the hope on the horizon for ALS, along with drugs now already under development or in clinical trials that are specifically targeted to patients with known genetic mutations. How far that horizon is in the distance, we dont know, but we can see it. We only wish Mr. Shepard and all our past patients could have reached that hopeful horizon.

Jeffrey D. Rothstein MD, PhD, a neurologist and professor at Johns Hopkins University, is the director of the universitys Brain Science Institute, ALS clinic and Robert Packard Center for ALS Research.

Read more from the original source:
Sam Shepard Died of ALS. Here's Why It's so Difficult to Treat. - Fortune

Skin Stem Cells Comments Off on Sam Shepard Died of ALS. Here’s Why It’s so Difficult to Treat. – Fortune | August 2nd, 2017

By Jacqueline Howard CNN

(CNN) -- Scientists are getting one step closer to snipping inherited genetic diseases out of human offspring using a gene-editing technique called CRISPR.

For the first time, scientists said, they corrected a gene mutation linked to inherited heart conditions in human embryos using the approach. A study demonstrating the technique was published in the journal Nature on Wednesday (PDF).

Last week, the MIT Technology Review released the first news of this scientific feat, describing the research as the first-known attempt at creating genetically modified human embryos in the United States.

However, Juan Carlos Izpisua Belmonte, a co-author of the study, described it as the first in the world to demonstrate gene-editing to be safe, accurate and efficient in correcting a pathogenic gene mutation in human embryos. Previous attempts by Chinese researchers were unsuccessful at achieving this without safety concerns.

"This is the first that has been demonstrated as safe and working," said Belmonte, a professor at the Salk Institute for Biological Studies' gene expression laboratory in La Jolla, California.

"All cells of the embryo were corrected," he said. "It seems to be working from these samples that we have chosen, but we need to do much more basic research with many other genes."

The study was a collaboration between the Salk Institute, the Oregon Health & Science University in Portland and Korea's Institute for Basic Science.

Scientists estimate that more than 10,000 human diseases may result from mutations to a single gene occurring in all cells of the body, according to the World Health Organization.

Cutting and correcting gene mutations

The study used 75 human zygotes in which the father carried a mutation on the MYBPC3 gene, Belmonte said. The eggs used to produce the zygotes did not carry that gene mutation. The researchers noted that they received informed consent from the donors of the eggs, sperm and embryos used in the study.

The goal was to correct a type of inherited heart condition. A mutation called MYBPC3 is associated with inherited heart conditions, including left ventricular noncompaction, familial dilated cardiomyopathy and familial hypertrophic cardiomyopathy, which affects an estimated one in 500 people worldwide.

Hypertrophic cardiomyopathy also is thought to be the most common inherited or genetic heart disease in the US, according to the Centers for Disease Control and Prevention.

In a lab dish, the researchers used CRISPR, a gene-editing technique, to remove the harmful MYBPC3 mutation from the human zygotes. Then, the zygotes' own DNA-repair mechanism replaced what was cut out with a copy of a MYBPC3 gene from the mother, which did not carry a mutation, Belmonte said.

"A male research subject known to be heterozygous for this gene mutation was recruited for the study, as were several healthy young egg donors," Dr. Paula Amato, an obstetrician-gynecologist at Oregon Health & Science University, said Tuesday. She was a co-author of the study.

"CRISPR was introduced at the time of sperm injection," she said. "Then, DNA repair of the embryos was assessed."

The researchers found that about 72% of zygotes were properly and safely corrected on the MYBPC3 gene, Belmonte said.

This method significantly differed from studies in which scientists used the CRISPR tool to manually replace what was cut out with whatever the scientists desired.

Researchers in China were the first to reveal attempts to modify genes in human embryos using CRISPR. Three separate studies were published in scientific journals describing Chinese experiments on gene editing in human embryos.

"The previous human studies done in China had very small numbers, and one of them used abnormal embryos," Amato said. "So we think this is the first, largest study from which you could draw some reasonable conclusions."

Some gene-editing attempts in human embryos have been problematic, resulting in an issue called mosaicism, in which the corrections made in one gene failed to replicate once that cell divided into two cells, those two cells divided into four cells and so on.

"So when the baby is born, all the cells do not have the mutation anymore. ... This study, it shows that we can correct the embryo and then, after the division, all the cells are corrected, so there's not what we call mosaicism," said Belmonte, who is also a member of the National Academies of Sciences, Engineering and Medicine's committee on human gene editing.

This year, the academies published a report on human genome editing that addressed potential applications of the technology, including the possible prevention or treatment of inherited diseases or conditions.

The future of gene editing

Though the researchers have expressed enthusiasm around their new study, they also noted that the findings must be replicated in followup research before this gene-editing approach can move forward to clinical trials.

"The fact that it is, apparently, a new and poorly understood mechanism and it is not the now standard CRISPR 'cut and replace' method adds to the time needed for research into its safety and effectiveness," said Hank Greely, professor of law and genetics at Stanford University, who was not involved in the new study.

Yet future research can come with some political challenges, Amato said.

"First of all, there are regulations regarding use of federal funds for embryo research, so the (US National Institutes of Health) does not currently support embryo research, so that's one barrier. The other barrier is, the (US Food and Drug Administration) is prohibited from considering any clinical trials related to germline genetic modification," she said.

In this new study the embryos were only allowed to mature to day three after fertilization before they were disaggregated, or isolated into various components, for further analysis.

In the far-off future, a clinical trial could include transplanting corrected embryos into a uterus with the goal of establishing pregnancy and then monitoring the embryos as they develop into children.

Still, "it is way too early to contemplate implanting the edited embryos for the purpose of actually establishing a pregnancy," said Dana Carroll, a professor of biochemistry at the University of Utah who was not involved in the new study but has used CRISPR in his own research.

"The genome editing tools are currently not sufficiently efficient and specific to be reliable, and regulatory and oversight processes have not been established," Carroll said, adding that the work on the new study was "well-done" and "well-presented."

"The authors have made an important discovery regarding the repair of CRISPR-induced DNA breaks in human eggs just at the time of fertilization," he said.

"This information will help to guide ongoing research, and it demonstrates that research on early-stage human embryos will be necessary to establish safe and effective procedures in the long run," he said. "There is still a lot of work to do to understand repair processes in very early embryos and to optimize the use of the CRISPR reagents, but this study makes a valuable contribution."

Some CRISPR critics have argued that gene editing may give way to eugenics and to allowing embryos to be edited with certain features in order to develop so-called designer babies.

However, the researchers wrote in their study that they hope CRISPR could be considered as an alternative option to preimplantation genetic diagnosis, also known as PGD, for couples at risk of passing on an inherited disease.

'This opens up the possibility for those embryos'

PGD, developed about a quarter-century ago, is a genetic testing procedure typically conducted after in vitro fertilization to diagnose a genetic disease or condition in an embryo before it is implanted.

Since the human genome contains two copies of each gene -- paternal and maternal alleles, or variant forms of genes -- a mutation affecting only one allele is called heterozygous.

When only one parent carries a heterozygous mutation on a gene, about half of the embryos from that parent should be mutation-free while the others would have the mutation. Selectively, the parents' doctor would chose the healthy embryos to be implanted and discard the embryos with the mutations, Belmonte said.

Sometimes, "a couple that wants to have a baby and they have a mutation, they may not have enough embryos to choose from," he said. This is when CRISPR can come in.

"This technology, independent of the embryos that are there, it would go on and correct all of them. ... This opens up the possibility for those embryos," he said. "That's important because after the first implantation, if it doesn't work, you can do it again."

The researchers wrote in their study, "PGD may be a viable option for heterozygous couples at risk of producing affected offspring. In cases when only one parent carries a heterozygous mutation, 50% of embryos should be mutant. In contrast, targeted gene correction can potentially rescue a substantial portion of mutant human embryos, thus increasing the number of embryos available for transfer."

Nonetheless, using CRISPR in that way remains a long way off.

Shoukhrat Mitalipov, director of the Oregon Health & Science University's Center for Embryonic Cell and Gene Therapy, helped lead the new study. In 2013, Mitalipov and his colleagues reported the first success in cloning human stem cells, reprogramming human skin cells back to their embryonic state. In 2007, a research team led by Mitalipov announced that they created the first cloned monkey embryo and extracted stem cells from it.

Now, when it comes to using CRISPR to correct gene mutations in embryos, Mitalipov said Tuesday, "We've done some ground work. ... There is still a long road ahead, and it's unclear at this point when we will be allowed to move on."

TM & 2017 Cable News Network, Inc., a Time Warner Company. All rights reserved.

See more here:
Scientists edit disease-causing gene mutation in human embryos - WENY-TV

Skin Stem Cells Comments Off on Scientists edit disease-causing gene mutation in human embryos – WENY-TV | August 2nd, 2017