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Jonathan Pitre battles blood, lung infections before second stem cell ... Ottawa Sun Jonathan Pitre is back in a Minneapolis hospital with blood and lung infections complications that will likely delay his second stem-cell transplant. Pitre and ... and more »

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Severely hyperbranched vascular network surrounding the spinal cord (red dotted box) of zebrafish embryo blood vessels in white.

A team of researchers at Karlsruhe Institute of Technology (KIT) shake at the foundations of a dogma of cell biology. By detailed series of experiments, they proved that blood vessel growth is modulated by neurons and not, as assumed so far, through a control mechanism of the vessel cells among each other. The results are groundbreaking for research into and treatment of vascular diseases, tumors, and neurodegenerative diseases. The study will be published in the journal Nature Communications.

Our work is pure basic research, Professor Ferdinand le Noble of KITs Zoological Institute says, but provides a completely new perspective on how blood vessels grow, branch out, or are inhibited in their growth. For decades, researchers have been looking for ways to promote or impede the formation of new blood vessels. Whereas heart attack and stroke patients would profit from new arteries, cancer patients would benefit from tumor starving by putting a stop to ingrowing blood vessels.

The key figures in the newly discovered extremely finely balanced process are signaling molecules: the brake on growth soluble FMS-like tyrosine kinase-1, referred to as 1sFlt1, and the vascular endothelial growth factor, referred to as VEGF. Even though, so far, it has been largely unknown how VEGF is regulated by the body, inhibition of this growth factor has been applied for years already in the treatment of cancer patients and of certain eye diseases. The therapy, however, is successful only in part of the patients and has several undesired side effects.

So far, research assumed the blood vessels to more or less regulate their own growth, explains le Noble. In case of oxygen deficiency, he points out, tissue, among others, releases the growth factor VEGF, thus attracting the blood vessels carrying VEGF receptors on their surfaces. We wanted to know how this blood vessel growth is regulated at the time of a creatures birth. The team around le Noble hence studied the continuous growth of nerve tracts and circulatory vessels in zebrafish model organisms. The eggs of zebrafish are transparent and develop outside of the mothers body, allowing researchers to watch and observe the development of organs or even individual cells without injuring the growing animal.

By means of fluorescent dyes, postgraduate Raphael Wild in a first step documented colonization of neuronal stem cells and subsequent vascular budding in the vertebral canal of zebrafish. To understand the exact process, the team started a detailed biochemical and genetic analysis.

The researchers proved that at different development stages, the nerve cells of the spinal cord produce more or less sFlt1 and VEGF and, in this way, modulate the development of blood vessels. At the early development stage, neuronal sFlt1 brakes blood vessel growth by binding and inactivating the growth factor VEGF. In the spinal cord, this creates an environment poor in oxygen, which is essential to the early development of the neuronal stem cells. With increasing nerve cell differentiation, concentration of the soluble sFlt1 decreases continuously, and the brake on vascular growth is loosened because more active VEGF is now available. Subsequently, blood vessels grow into the young spinal cord to provide it with oxygen and nutrients.

In addition, Raphael Wild and his colleague Alina Klems show that the concentration of the growth factor is crucial as regards the density of the developing blood vessel network. Whereas, when the brake sFlt1 in nerve cells was switched off completely, a dense network of blood vessels formed which even grew into the vertebral canal, the growth of blood vessels was suppressed when sFIt1 was increased. Even small variations in substance concentration thus led to severe vascular developmental disorders.

Since vascular cells also have own forms of sFlt1 and VEGF, the question arose as to whether blood vessel growth may, to a certain degree, regulate itself. To find out, the researchers applied the still young and extremely elegant CRISPR/Cas method: Whereas there was no effect when sFlt1 was switched off only in vascular cells, an intensive growth of blood vessels was observed when the production of sFlt1 was switched off in the nerve cells only.

From the results we conclude that by a fine modulation of sFlt1 and VEGF, nerve cells very dynamically regulate the density of their blood vessel network according to requirements or according to the respective development stage, le Noble points out. The previous assumption that growing blood vessel cells control the succeeding vascular cells is a cell biology dogma whose foundations are being shaken.

Please note: The content above may have been edited to ensure it is in keeping with Technology Networks style and length guidelines.

References:Wild, R., Klems, A., Takamiya, M., Hayashi, Y., Strhle, U., Ando, K., Mochizuki, N., van Impel, A., Schulte-Merker, S., Krueger, J., Preau, L. and le Noble, F. (2017) Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization, Nature Communications, 8, p. 13991. doi: 10.1038/ncomms13991.

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Cells within our bodies divide and change over time, with thousands of chemical reactions occurring within each cell daily. This makes it difficult for scientists to understand whats happening inside. Now, tiny nanostraws developed by Stanford researchers offer a method of sampling cell contents without disrupting its natural processes.

Nicholas Melosh, associate professor of materials science and engineering, developed a new, non-destructive system for sampling cells with nanoscale straws. The system could help uncover mysteries about how cells function. (Image credit: L.A. Cicero)

A problem with the current method of cell sampling, called lysing, is that it ruptures the cell. Once the cell is destroyed, it cant be sampled from again. This new sampling system relies on tiny tubes 600 times smaller than a strand of hair that allow researchers to sample a single cell at a time. The nanostraws penetrate a cells outer membrane, without damaging it, and draw out proteins and genetic material from the cells salty interior.

Its like a blood draw for the cell, said Nicholas Melosh, an associate professor of materials science and engineering and senior author on a paper describing the work published recently in Proceedings of the National Academy of Sciences.

The nanostraw sampling technique, according to Melosh, will significantly impact our understanding of cell development and could lead to much safer and effective medical therapies because the technique allows for long term, non-destructive monitoring.

What we hope to do, using this technology, is to watch as these cells change over time and be able to infer how different environmental conditions and chemical cocktails influence their development to help optimize the therapy process, Melosh said.

If researchers can fully understand how a cell works, then they can develop treatments that will address those processes directly. For example, in the case of stem cells, researchers are uncovering ways of growing entire, patient-specific organs. The trick is, scientists dont really know how stem cells develop.

For stem cells, we know that they can turn into many other cell types, but we do not know the evolution how do they go from stem cells to, say, cardiac cells? There is always a mystery. This sampling technique will give us a clearer idea of how its done, said Yuhong Cao, a graduate student and first author on the paper.

The sampling technique could also inform cancer treatments and answer questions about why some cancer cells are resistant to chemotherapy while others are not.

With chemotherapy, there are always cells that are resistant, said Cao. If we can follow the intercellular mechanism of the surviving cells, we can know, genetically, its response to the drug.

The sampling platform on which the nanostraws are grown is tiny about the size of a gumball. Its called the Nanostraw Extraction (NEX) sampling system, and it was designed to mimic biology itself.

In our bodies, cells are connected by a system of gates through which they send each other nutrients and molecules, like rooms in a house connected by doorways. These intercellular gates, called gap junctions, are what inspired Melosh six years ago, when he was trying to determine a non-destructive way of delivering substances, like DNA or medicines, inside cells. The new NEX sampling system is the reverse, observing whats happening within rather than delivering something new.

Its a super exciting time for nanotechnology, Melosh said. Were really getting to a scale where what we can make controllably is the same size as biological systems.

Building the NEX sampling system took years to perfect. Not only did Melosh and his team need to ensure cell sampling with this method was possible, they needed to see that the samples were actually a reliable measure of the cell content, and that samples, when taken over time, remained consistent.

When the team compared their cell samples from the NEX with cell samples taken by breaking the cells open, they found that 90 percent of the samples were congruous. Meloshs team also found that when they sampled from a group of cells day after day, certain molecules that should be present at constant levels remained the same, indicating that their sampling accurately reflected the cells interior.

With help from collaborators Sergiu P. Pasca, assistant professor of psychiatry and behavioral sciences, and Joseph Wu, professor of radiology, Melosh and co-workers tested the NEX sampling method not only with generic cell lines, but also with human heart tissue and brain cells grown from stem cells. In each case, the nanostraw sampling reflected the same cellular contents as lysing the cells.

The goal of developing this technology, according to Melosh, was to make an impact in medical biology by providing a platform that any lab could build. Only a few labs across the globe, so far, are employing nanostraws in cellular research, but Melosh expects that number to grow dramatically.

We want as many people to use this technology as possible, he said. Were trying to help advance science and technology to benefit mankind.

Melosh is also a professor in the photon science directorate at SLAC National Accelerator Laboratory, a member of Stanford Bio-X, the Child Health Research Institute, the Stanford Neurosciences Institute, Stanford ChEM-H and the Precourt Institute for Energy. Wu is also the Simon H. Stertzer, MD, Professor; he is director of the Stanford Cardiovascular Institute and a member of Stanford Bio-X, the Child Health Research Institute, Stanford ChEM-H and the Stanford Cancer Institute. Pasca is also a member of Stanford Bio-X, the Child Health Research Institute, the Stanford Neurosciences Institute and Stanford ChEM-H.

The work was funded by the National Institute of Standards and Technology, the Knut and Alice Wallenberg Foundation, the National Institutes of Health, Stanford Bio-X, the Progenitor Cell Biology Consortium, the National Institute of Mental Health, an MQ Fellow award, the Donald E. and Delia B. Baxter Foundation and the Child Health Research Institute.

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February 21, 2017 by Mark Derewicz Top Row: Heart arteries in normal mice, diabetic mice, and normal mice with deleted IRS-1 gene. Bottom row: when artery is wounded, diabetic mice with less IRS-1 and normal mice with deleted IRS-1 gene show much greater blockage due to over-proliferation of smooth muscle cells. Credit: Clemmons Lab, UNC School of Medicine

People with diabetes are at high risk of developing heart disease. Despite knowing this, scientists have struggled to trace the specific biology behind that risk or find ways to intervene. Now, UNC School of Medicine researchers have hunted down a possible culprit - a protein called IRS-1, which is crucial for the smooth muscle cells that make up veins and arteries.

According to a study published in the Journal of Biological Chemistry, too little of IRS-1 causes cells to revert to a "dedifferentiated" or stem-cell like state, and this may contribute to the buildup of plaque in the heart's arteries, a condition known as atherosclerosis, which increases the risk of heart attack, stroke, and other forms of heart disease.

"When diabetes is poorly managed, your blood sugar goes up and the amount of this protein goes down, so the cells become subject to abnormal proliferation," said senior author David R. Clemmons, MD, Sarah Graham Kenan Professor of Medicine at the UNC School of Medicine. "We need to conduct more studies, but we think this cell pathway may have significant implications for how high blood glucose leads to atherosclerosis in humans."

The research could bring scientists one step closer to finding drugs to help stave off heart disease in people with diabetes, who are twice as likely to have heart disease or experience a stroke, as compared to people without diabetes. People with diabetes also tend to experience major cardiac events at a younger age.

The study focused on the cells that form the walls of veins and arteries, known as vascular smooth muscle cells. The main function of these cells is to contract whenever the heart beats, helping to push oxygen-rich blood to the body's tissues. When plaque builds up along the arterial walls, these cells gradually lose their ability to contract.

In their previous work, Clemmons and colleagues discovered that diabetes can trigger an abnormal cell signaling pathway that causes vascular smooth muscle cells to proliferate, which contributes to atherosclerosis. But their attempts to correct the abnormal signaling pathway didn't seem to completely solve the problem, leading them to suspect another factor.

In the new study, the team found that IRS-1 acts as an inhibitor of the abnormal signaling pathway thereby keeping the vascular smooth muscle cells differentiated, or specialized. In the absence of IRS-1, the cells revert to a stem-cell like state, which in turn activates the abnormal signaling pathway and promotes cell proliferation.

In people with diabetes, the presence of IRS-1 is strongly influenced by how well - or how poorly - blood sugar is kept in check. Previous studies have shown that patients who frequently or consistently have high blood sugar show dramatic reductions in IRS-1. The new study is the first to link this reduction with a predisposition for heart disease.

"The study suggests that you can't just inhibit the abnormal signaling, which we've already figured out how to do," Clemmons said. "Our work suggests you probably have to restore the normal signaling pathway, at least to some extent, in order to completely restore the cells to normal cell health, differentiation, and functioning."

As a next step, the Clemmons lab will look for things that might stimulate the synthesis of this protein even in the presence of high blood glucose.

To prove that IRS-1 acts as a brake on the abnormal signaling pathway that leads to cell proliferation, the team conducted experiments in three different types of mice: healthy mice, diabetic mice, and nondiabetic mice that were genetically engineered to produce no IRS-1. The scientists made a small incision in the blood vessels of the animals and then watched to see how the vascular smooth muscle cells reacted. In healthy mice, the incision stimulated wound healing but little cellular proliferation. In both the diabetic animals and the nondiabetic IRS-1 deficient animals, the researchers observed a marked increase in abnormal cellular proliferation.

The findings suggest that it may be possible to counteract the deleterious effects of high blood sugar on atherosclerosis by developing drugs that boost IRS-1.

Clemmons said the activities of IRS-1 might also play a role in other diabetes complications, such as eye and kidney disease. The researchers plan to study those potential links.

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Why do some people get Type 2 diabetes, while others who live the same lifestyle never do?

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I was diagnosed with type 2 Diabetes and put on Metformin on June 26th, 2016. I started the ADA diet and followed it 100% for a few weeks and could not get my blood sugar to go below 140. Finally i began to panic and called my doctor, he told me to get used to it. He said I would be on metformin my whole life and eventually insulin. At that point i knew something wasn't right and began to do a lot of research. On August 13th I found Lisa's diabetes story (google " HOW EVER I FREED MYSELF FROM THE DIABETES " ) I read that article from end to end because everything the writer was saying made absolute sense. I started the diet that day and the next morning my blood sugar was down to 100 and now i have a fasting blood sugar between Mid 70's and the 80's. My doctor took me off the metformin after just three week of being on this lifestyle change. I have lost over 30 pounds and 6+ inches around my waist in a month

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This colored scanning electron micrograph (SEM) is showing the internal structure of a broken finger bone. Here, the periosteum (outer bone membrane, pink), compact bone (yellow) and bone marrow (red), in the medullary cavity, can be seen. Photo Credit: STEVE GSCHMEISSNER/Science Photo Library/Getty Images

Updated July 15, 2016.

Bone marrow is the soft, flexible connective tissue within bone cavities. A component of the lymphatic system, bone marrow functions primarily to produce blood cells and to store fat. Bone marrow is highly vascular, meaning that it is richly supplied with a large number of blood vessels. There are two categories of bone marrow tissue: red marrow and yellow marrow. From birth to early adolescence, the majority of our bone marrow is red marrow.

As we grow and mature, increasing amounts of red marrow is replaced by yellow marrow. On average, bone marrow can generate hundreds of billions of new blood cells every day.

Bone marrow is separated into a vascular section and non-vascular sections. The vascular section contains blood vessels that supply the bone with nutrients and transport blood stem cells and mature blood cells away from the bone and into circulation. The non-vascular sections of the bone marrow are where hematopoiesis or blood cell formation occurs. This area contains immature blood cells, fat cells, white blood cells (macrophages and plasma cells), and thin, branching fibers of reticular connective tissue. While all blood cells are derived from bone marrow, some white blood cells mature in other organs such as the spleen, lymph nodes, and thymus gland.

The major function of bone marrow is to generate blood cells. Bone marrow contains two main types of stem cells. Hematopoietic stem cells, found in red marrow, are responsible for the production of blood cells.

Bone marrow mesenchymal stem cells (multipotent stromal cells) produce the non-blood cell components of marrow, including fat, cartilage, fibrous connective tissue (found in tendons and ligaments), stromal cells that support blood formation, and bone cells.

In adults, red marrow is confined mostly to skeletal system bones of the skull, pelvis, spine, ribs, sternum, shoulder blades, and near the point of attachment of the long bones of the arms and legs. Not only does red marrow produce blood cells, but it also helps to remove old cells from circulation. Other organs, such as the spleen and liver, also filter aged and damaged blood cells from the blood. Red marrow contains hematopoietic stem cells that produce two other types of stem cells: myeloid stem cells and lymphoid stem cells. These cells develop into red blood cells, white blood cells, or platelets. (See, bone marrow stem cells).

Yellow marrow consists primarily of fat cells. It has poor vascular supply and is composed of hematopoietic tissue that has become inactive. Yellow marrow is found in spongy bones and in the shaft of long bones. When blood supply is extremely low, yellow marrow can be converted to red marrow in order to produce more blood cells.

If bone marrow becomes damaged or diseased, it can result in low blood cell production. Bone marrow disease can develop from bone marrow and blood cancers such as leukemia. Radiation exposure, certain kind of infections, and diseases such as aplastic anemia and myelofibrosis can also cause blood and marrow disorders. These diseases compromise the immune system and deprive organs and tissues of the life giving oxygen and nutrients they need. A bone marrow transplant may be done in order to treat blood and marrow diseases. In the process, damaged blood stem cells are replaced by healthy cells obtained form a donor. The healthy stem cells can be obtained from the donor's blood or bone marrow. Bone marrow is extracted from bones such as the hip or sternum. Stem cells may also be obtained from umbilical cord blood to be used for transplantation.

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TEMPE, Ariz. On the day he hoped would save his elbow, Garrett Richards laid face down on a table with his back exposed. A doctor guided a needle into the iliac crest of his pelvic bone and began to extract bone marrow. Richards was wide awake, the blessing of local anesthesia saving him from physical pain but not the anxiety that crept into his head: Is this really going to work?

Within a few minutes, the harvested marrow was hurried to a centrifuge, spun to separate the good stuff, mixed into a slurry of platelet-rich plasma and readied to inject into Richards damaged right elbow. Rather than the standard tear across his ulnar collateral ligament, Richards ran lengthwise along the middle of his UCL, a rare manifestation of an increasingly commonplace injury that almost always ends with Tommy John surgery. Not in this case. While he could have chosen that route, he wanted to explore first the efficacy of the aforementioned good stuff: stem cells.

Today, Garrett Richards is darting 98-mph fastballs again. I feel as good as I ever have throwing a baseball, he said Monday from Tempe Diablo Stadium, where the Los Angeles Angels, perhaps the most Tommy John-addled team in baseball, expect to break camp with Richards as their opening day starter. The 28-year-old is the latest player to turn to orthobiologics, the class of treatments that includes stem cells and PRP, in hopes of healing an injury. While clinical studies have shown great success with those who use orthobiologics, they are not yet a panacea for the pervasive elbow injuries in baseball for two reasons: They work only on partial ligament tears, like Richards, and medical studies have yet to validate their efficacy independent of other treatments run concurrently.

The lack of knowledge as to how orthobiologics work inside the body while the proteins in stem cells and platelets are believed to regrow damaged tissue, doctors have yet to isolate best practices for particular injuries speaks to the difficulties in true medical advances. Still, the desire of Richards and others to avoid surgery lends orthobiologics enough credence to warrant further studies.

I truly think this kind of treatment has significant potential, said Dr. Neal ElAttrache, a longtime orthopedic surgeon at the Kerlan-Jobe clinic in Los Angeles who introduced orthobiologics to Major League Baseball when he injected PRP into the elbow of Dodgers reliever Takashi Saito in 2008. Theres no question biologics are here to stay and biologic manipulation is the frontier of treatment in what were doing. The problem, as I see it, is that the marketing and clinical use has far exceeded the science behind it.

Translation: Once the use of PRP and stem cells found traction in the media, pro athletes and weekend warriors alike sought their use, even if the success stories skewed anecdotal. Bartolo Colon resurrected his career after a stem cell injection in 2010 and is still pitching today at 43. Others did so without the fanfare or publicity. Richards faced a choice after being diagnosed with a partially torn UCL last May: Undergo Tommy John surgery and, at earliest, return following the 2017 All-Star break or follow the advice of Dr. Steve Yoon, a partner of ElAttraches at Kerlan-Jobe, and try to salvage the ligament with stem cells.

Science, bro, Richards said. Im a believer now.

Two weeks before Richards began his treatment, teammate Andrew Heaney had looked to avoid Tommy John via stem cells. Richards figured theyd rehab together every step of the way and be back in time for the fall instructional league. Then at the end of June, a scan showed Heaneys elbow wasnt healing, and he would need reconstructive surgery. Already Tyler Skaggs had taken nearly two years to return from his 2014 surgery, and six weeks after Heaneys, starter Nick Tropeano went down. Like Heaney, he is expected to miss the 2017 season.

It made Richards recovery that much more imperative. His first checkup, six weeks in, showed regrowth in the torn area via ultrasound. By August, he started throwing, and come October, when instructional league was in full bloom, so too was Richards. He didnt hesitate to pump his fastball and rip off one of his spin-heavy breaking balls. As far as pure, raw stuff goes, few in baseball can match Richards.

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He was convinced science was working, bro, though the skepticism about orthobiologics generally remains, and understandably so, in the medical community. In May 2013, a paper published in the American Journal of Sports Medicine found 30 of 34 overhand throwers with partial UCL tears who used PRP had returned to their previous level of competition. This was reason for celebration. If a player could avoid the 14-month-plus recovery from the surgery, better for him as well as the team.

Another study arrived in 2016 that didnt cast doubt on the value of orthobiologics so much as offer a different avenue: rest. The 28 players used everything from electrical stimulation, ultrasound, laser therapy, massage and other soft-tissue work. And when paired with rest, their return to previous level came in at 84 percent. It was almost exactly as effective as PRP.

This reinforced ElAttraches concern: Neither of those studies had a control group against which to measure, so the numbers, while impressive, could not isolate what helped and what didnt. This chicken-or-egg question struck ElAttrache just the same when Saito returned and went on to pitch five seasons.

Maybe it was the injection, ElAttrache said. Or maybe it was that we shut him down and let him heal.

Garrett Richards is darting 98-mph fastballs again after turning to orthobiologics. (Getty Images)

He doesnt know, and thats an important distinction as orthobiologics grows exponentially. In 2004, voters in California pledged to provide $3 billion for stem-cell research and create the California Institute of Regenerative Medicine. It remains a benefactor for an industry trying to find its place in the United States.

Across the world, stem cells have far greater potency. U.S. law prevents doctors from manipulating the cells in any way. They are extracted and put back into patients bodies as is. In Switzerland, for example, doctors will harvest stem cells, manipulate them to promote greater healing capacity and then inject them. At least one star pitcher this offseason sought a stem cell injection in the United States, according to sources, while another veteran traveled halfway across the world to Zurich, seeking the comparative lack of regulations just as Peyton Manning did in 2011 to help heal a neck injury that eventually needed surgery.

The future of orthobiologics domestically doesnt end with the FDA loosening rules on stem cell usage. Doctors see significant promise in stem cells from a babys umbilical cord or a mothers placenta, both of which can be frozen. Already theyre capable of harvesting stem cells from old patients and engineering the cells into an immature state. The possibilities going forward are endless.

For right now, theyre going to play themselves out in Anaheim. The danger zone for re-injury after using orthobiologics tends to fall between April and June, though Richards cant imagine falling prey again. In addition to the 13-week break from throwing he took over the summer, Richards spent 10 more weeks in the offseason letting it heal further.

During his down time, Richards studied his own delivery to find even the slightest inefficiencies. He had three numbers in mind. The first was 85. Thats the percent at which he said hell throw his fastball, though because of improved mechanics he expects it wont hinder his velocity. The second is 100. Thats the pitch limit the Angels will foist on Richards, and hes not one to fight. The third is 200. Thats the number of innings Richards wants to pitch this season. He did it in 2015 and sees no reason he cant again.

If he can throw 85 percent, keep his pitch count below 100 and get those 200 innings, it will play publicly as another validation of orthobiologics. Just the same, if Richards elbow gives out eventually, his association with stem cells could perhaps give those considering it pause. Richards pays no mind to this. He just wants to be great.

So much so, in fact, that its going to cost him. Inside the Angels clubhouse, a chart, labeled 1 through 13, is taped to the side of a locker. Its a list of shame with the price buying lunch for the entire team. Players, coaches, P.R. directors, even manager Mike Scioscia are on there. Next to No. 6, it read: G. Rich Ace. He had made the mistake of saying aloud what he believed to be true: that hes the ace of the Angels.

Fulfilling that depends on plenty of things, none as important as his elbow, and Richards knows that. Hell do everything he can to take care of it, to nurture it, to fight against its natural gift of velocity that puts him at such risk. To make sure that next time hes on a table in the doctors office, its not with his elbow opened up and another season lost.

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Cellect Announces Positive Clinical Trial Results P&T Community Dr. Yaron Pereg, Cellect's Chief Development Officer, commented: These results from processing human stem cells for bone marrow transplantation using ApoGraft clearly demonstrated that Cellect's proprietary platform could improve the outcome of stem ... Early-stage study validates Cellect Bio's method of stem cell selection; shares ahead 19%Seeking Alpha all 5 news articles »

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Jonathan Pitre battles blood, lung infections before second stem cell transplant Ottawa Citizen People with RDEB have a fault in the gene responsible for a specific kind of collagen that connects the outer layer of skin, the epidermis, with those below it. The clinical trial seeks a biochemical correction to that fault. If the transplant works ...

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Scientist Juan Carlos Izpisua Belmonte from the Salk Institute in La Jolla, California, claims that the aging process may reversible: Our study shows that aging may not have to proceed in one single direction. With careful modulation, aging might be reversed.

Izpisua Belmonte attests that he implemented a new form of gene therapy on mice that were given a genetic disorder called progeria. After six weeks of treatment, the animals looked youngerand not only that, they had straighter spines, better cardiovascular health, healed more quickly when injured and actually lived longer.

How Its Done The rejuvenating treatment performed on the mice manipulates adult cells, such as skin cells, and turns them back into powerful stem cells (similar to what is seen in embryos). These powerhouses are referred to as induced pluripotent stem (iPS) cells and have the ability to multiply and transform into any cell type in the body; in fact, in trial tests, Izpisua Belmonte says iPS cells are being designed to provide organs and limbs for patients. He claims that his latest study is the first to show that the same technique can be used on other cells to rewind the clock and make them look younger. Izpisua Belmonte explains, The treatment involved intermittently switching on the same four genes that are used to turn skin cells into iPS cells. The mice were genetically engineered in such a way that the four genes could be artificially switched on when the mice were exposed to a chemical in their drinking water.

What This Means: This finding at the Salk Institute suggests that aging may not have to proceed in one directionin fact, Izpisua Belmonte states that it may actually be reversible. Although tests have not been conducted on humans yet, he predicts that applications via creams or injections are a decade away.

This rejuvenating treatment may not lead to immortality, but due to a growing body of evidence, scientists at the Salk Institute theorize that aging is driven by an internal genetic clock that actively causes our body to enter a state of decline. In developing this technology, it is hoped that future treatments designed will slow the ticking of this internal clock and ultimately increase life expectancy.

Whats the Catch? Dr. Sidney Chiu, a 5th year resident at the University of Toronto, thinks this information should be taken with a grain of salt: The findings are promising, but nowhere near ready for the front lines of healthcare. These experiments were done in highly controlled settings on genetically modified mice. If this finding were true, it would be worthy of a Nobel Prize because it would be akin to uncovering the Holy Grail. Chiu elaborates, If you can induce iPS cells, you have the basic building blocks to regenerate anything in the body. But this is far beyond any current medical science we have.

There are also numerous issues to address concerning the study: firstly, the mice are bred in labs for these types of tests, so the variables are controlled from the outset to attain desired results. Chiu adds, In the real world, you cannot turn specific genes on and off using treated water on mice in the wild, let alone humans. There isnt one specific gene for aging; I would be cautious about this scientists claims that isolating merely four could unlock the key to anti-aging. Even if we were just talking about reviving skin tissue, if his findings were true, it would be a breakthrough.

Chiu says that while it is technically possible to alter genetic material when humans are in an embryonic state, that wasnt done here (gene editing research in human embryos is currently allowed in Sweden China, and the United Kingdom. The United States doesnt currently have any legal prohibitions against it).

But its not to say that all of this is in the realm of science fiction; Chiu offers knowledge of research being conducted specifically for telomeres and their relationship to aging. Think of telomeres as the plastic caps that protect your shoelaces from fraying. The laces would be our chromosomes, the recipe for making a living thing. In fact, telomeres have an important role; they protect genetic material from damage that could otherwise lead to diseases or cell death. But because the number of cell divisions in telomeres is finite, once they become shorter (in length) and can no longer reproduce, it causes tissues to degenerate and eventually die. It is theorized that this process may contribute to the human aging process. So scientists are trying to find ways to extend the length of telomeres.

Izpisua Belmonte says that chemical approaches (via creams or injections) might be in human clinical trials to rejuvenate skin, bones and muscle within the next decade. However, from his perspective as a frontline healthcare worker, Chiu believes that we may just have to wait a bit longer than that before such innovations are accessible to everyone.

Main Photo by Thomas Rydberg, CC-BY

Tiffany Leigh is a Toronto-based food, travel, and science writer.

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What's the Catch: The Fountain of Youth - Paste Magazine

IPS Cell Therapy Comments Off on What’s the Catch: The Fountain of Youth – Paste Magazine | February 21st, 2017

The Register's editorial 5:32 p.m. CT Feb. 20, 2017

A tray of vials containing cerebral spinal fluid in Baltimore used to analyze both adult and fetal tissue in cancer research.(Photo: AP)

Among the threats to scientific advances are politicians who do not understand science. Unfortunately, too many of these politicians land jobs in the Iowa Legislature. They send a message this state is the last place a medical researcher should locate.

In 2002, lawmakers with an unfounded fear of scientists cloning babies passed a bill banning the creation of stem cells through a process called somatic cell nuclear transfer. Researchers useembryos, left over from in vitro fertilization, that would otherwise be discarded. After the vote banning the process, lawmakers were crying, hugging and carrying on about how life begins at conception.

Their emotion was pathetically misguided, as there was nothing pro-life about the measure. In fact, the law jeopardized life-saving research. It also prompted a cell biologist at the University of Iowa to pack up, move to Illinois and take her team and millions of federal dollars for cancer research with her.

Now here we go again. Lawmakers who apparently lack anunderstanding of laboratory research and the history of medical advancementsare pushing Senate File 52 in yet another effort to meddle in the work of real scientists. The bill, recently approved by a GOP-led Senate subcommittee,would ban acquiring, providing, receiving, otherwise transferring or using fetal tissue in this state. Fetal tissue, extracted during legal, voluntary abortions, can be discarded or used in medical research.

Lawmakers apparently would rather it be discarded. Committee chair Sen. Jake Chapman, R-Adel, said he didn't want to hinder research, but we also need to understand there is a moral responsibility, as well, to ensure that baby body parts arent being sold.

The same way no one was cloning babies in Iowa more than a decade ago, no one is selling "baby parts" today.

But inflammatory rhetoric is what people resortto when they don't want to acknowledge facts. Federal law already prohibits profiting from selling fetal tissue. Planned Parenthood of the Heartland says its Iowa affiliate does not even donate it. If the bill becomes law, anyone using fetal tissue namely researchers could land in the slammer for up to 10 years.

The Iowa Board of Regents registered opposition to the legislation, along with lobbyists representing the medical industry, churches and others. The board, which oversees state universities, requested an exemption that would allow research on certain fetal cells and proposed language to enable medical donations and permit the diagnosis of diseases.

Lawmakers did not immediately amend the bill, even thoughUI has been one of dozens of institutions across the country that has used fetal tissue in medical research. In recent years, the National Eye Institute provided the school more than $1 million for glaucoma research that used the tissue, according to data compiled by the Associated Press in 2015.

Fetal tissue has been successfully used for decades in medical research. It was critical in creating a vaccine for polio, a disease that crippled, paralyzed and sometimes killed its victims. Scientistsinfected fetal kidney cellsto produce mass quantities of the virus that were collected, purified and used for inoculations. They won a Nobel Prize for Medicine in 1954.

Research using human fetal cells shows promise in treatments for spinal cord injuries, eye disease, strokes and Parkinson's disease. But some Iowa lawmakers appear uninterested in saving and improvinglives.They are, however, interested in catering to theanti-abortion crowd with a bill that would not prevent a single abortion.

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Editorial: Fetal tissue bill is anti-life, anti-science - DesMoinesRegister.com

Spinal Cord Stem Cells Comments Off on Editorial: Fetal tissue bill is anti-life, anti-science – DesMoinesRegister.com | February 20th, 2017

The disease is caused by the immune system malfunctioning and mistakenly attacking nerve cells in the brain and spinal cord.

It leads to problems with movement, vision, balance and speech.

The treatment, autologous hematopoietic stem cell transplantation (AHSCT), was given to patients with advanced forms of the disease who had failed to respond to other medications.

A similar approach has been trialed on people with certain forms of cancer, with encouraging early results.

Dr Paolo Muraro, the new study's lead author, said: "We previously knew this treatment reboots or resets the immune system but we didn't know how long the benefits lasted.

"In this study, which is the largest long-term follow-up study of this procedure, we've shown we can 'freeze' a patient's disease - and stop it from becoming worse, for up to five years."

The researchers noted, however, that the nature of the treatment, which involves aggressive chemotherapy, carried significant risks.

The chemotherapy deactivates the immune system for a short period of time, which can lead to greater risk of infection - of the 281 patients who received AHSCT, eight died in the 100 days after treatment.

The treatment works by destroying the immune cells responsible for attacking the nervous system.

Patients were given a drug which encourages stem cells to move from the bone marrow into the bloodstream, where they were removed from the body.

High-dose chemotherapy was then administered to kill all immune cells, before the patient's own stem cells were put back into the body to "reset" the immune system.

Nearly three in four (73%) patients with relapsing MS - where the disease flares up before symptoms improve - found their symptoms did not worsen for five years after having AHSCT, compared with one in three patients with progressive MS, the more severe variant of the disease.

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New stem cell treatment 'freezes' multiple sclerosis - Telegraph.co.uk

Bone Marrow Stem Cells Comments Off on New stem cell treatment ‘freezes’ multiple sclerosis – Telegraph.co.uk | February 20th, 2017

JACKSONVILLE, Fla. As a boy growing up in Kano, Nigeria, Dr. Abba Zubair dreamed of going to space.

On Sunday, his work hitched a ride with a private rocket blasting off from NASA's Kennedy Space Center in Cape Canaveral, Fla., on a trip to the International Space Station.

Dr. Zubair, an associate professor of laboratory medicine and pathology at the Mayo Clinic's Florida campus, prepared a science package involving stem cells as part of a resupply mission to the ISS aboard a SpaceX Falcon 9 rocket.

"It was my first rocket launch view," said Dr. Zubair, who was on hand to watch and listen to the deafening sound as his experiment rode into space. "It was incredible."

The stem cells -- specialized cells derived from bone marrow come from Dr. Zubair's lab. Dr. Zubair, according to a report from the Mayo Clinic, specializes in cellular treatments for disease and regenerative medicine. He hopes to find out how the stem cells hold up in space and if they can be more quickly produced in microgravity.

More specifically, Zubair said, he is hoping the research can help in treatment of patients who have suffered a stroke-related brain injury.

"Stem cells are known to reduce inflammation," he said in a press release. "We've shown that an infusion of stem cells at the site of stroke improves the inflammation and also secretes factors for the regeneration of neurons and blood vessels."

The problem with such a treatment and studying the treatment is generating enough stem cells for the job. Based on current regenerative medicine studies, patients need at least 100 million stem cells for an effective dose. However, reproducing stem cells can be time consuming since the cells naturally limit their numbers.

"Scalability is a big issue," Dr. Zubair said. "I've been interested in a faster way to make them divide."

And on earth, everything is impacted by gravity, from how high we grow to our bone size and other physiological traits. "So, how can we use the effect of gravity to impact how the cells divide?" he asked.

Experiments that simulate stem cell growth in microgravity, thus far, have shown cells do grow more quickly than experimental controls, he said. So he began working toward getting an experiment into space. The experiment needed to be designed so the crew onboard the space station could run the experiment with some simple training, and Dr. Zubair will be able to watch the experiment in real time via a video connection. "We'll get some data as early as next week," he said.

If all goes well, growing stem cells in space something Dr. Zubair admits sounds like a dream of the distant future might become a reality more quickly than many people think.

"There are some companies interested in floating labs," he said. "I think the future is bright. There are a lot of possibilities in the area of regenerative medicine."

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Mayo doc's stem cell experiment blasts into space - Post-Bulletin

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February 18, 2017 at 1:00 am | By Lisa Turpin Special to the News-Press

National Donor Day, observed on Feb. 14, is a great time to register as an organ, eye, and tissue donor or to make an appointment to donate blood or platelets.

What could show more love on Valentines Day than the act of giving ones body to help another?

Whether you are a living donor of blood products, stem cells, kidney or liver, register with your state as an organ donor, or make the decision for your loved one to be a donor, you are truly giving the gift of life.

Nationally, more than 119,000 people are waiting for an organ transplant, including 2,091 children.

That doesnt include the number waiting for a bone marrow (stem cell) matched donor which is much more complicated to find.

Significant progress continues in the advancement of transplantation medicine with goals of lengthening life spans, restoring function, appearance, and quality of life.

But it still takes the generosity of donors and their loved ones to make a transplant possible.

Claudia Swigart of Pinehurst believes the true value of organ donation is the gift of time.

In her case, fifteen years with her husband Wendell that she, their five combined children, thirteen grandchildren, and twelve great-grandchildren may not have had.

Wendell and his three siblings all had Polycystic Kidney Disease (PKD), an inherited condition causing cysts to form in the kidney causing damage and kidney failure.

Wendell worked in the mine here in the Valley, shares Claudia.

He found out he had Polycystic Kidney Disease when he was thirty-four and he was careful, he exercised, ate healthy and never smoked. He didnt have any kidney problems until he was sixty-three and had to have open heart surgery.

The surgery was hard on Wendell and his lungs collapsed, he nearly died and it put his kidneys in distress.

He started dialysis after that and was eventually put on the kidney transplant list to receive a transplant at Sacred Heart Medical Center.

The dialysis center in Pinehurst had not opened, so Claudia drove Wendell to Coeur dAlene two times a week for three-hour treatments.

Claudia shared, I am so thankful they opened a dialysis center here. Its exhausting enough to be on dialysis without the traveling.

But there is more to this story.

We always liked telling everyone we could about what happened because we knew God had His hand in the plan, explains Claudia.

They normally traveled to Arizona in their camper for the winter.

Wendell would arrange to have dialysis at the center in Arizona instead of Coeur dAlene.

Well, in 2001 we were planning on leaving so Wendell called to remove himself from the transplant list while we were gone. But, when he called to arrange dialysis at the center in Arizona, they were full! said Claudia.

Since Wendell couldnt have dialysis in Arizona, they were forced to stay home which meant he remained on the transplant list.

Just a few weeks later we got the call! Claudia exclaimed.

Wendell was told he had a matched kidney on the way from a donor in Alaska.

Wendell was sixty-five at the time and he asked if there were any younger people waiting for transplants, anyone still raising young kids who needed it more than he did. His doctor knew he was that kind of man and firmly told him that it was Wendells kidney and he was taking it!

Wendells kidney was such a good match he never experienced any problems or symptoms of rejection.

The transplant coordinators said that the Swigarts could write a letter to the donors family in Alaska if they wanted to have communication with them or thank them.

We wrote a letter to the family two months later and Wendell told them he would take real good care of the kidney, Claudia said.

Wendell did take great care of himself but unfortunately fought esophageal cancer unrelated to his kidneys and passed away in March of 2016 at the age of 80.

The donors family never wrote back, so they do not know the identity of the donor, but Claudia and Wendell were glad they sent the thank-you letter.

We went back to Arizona the year after the transplant and didnt have to worry about dialysis any more. We may never have gotten to do that and he sure wouldnt have had the life he had without the generosity of the donor and their family.

Wendell Swigart had 15 extra quality years with his bride and they celebrated their forty-sixth wedding anniversary before his passing.

Statistics say that only three out of 1,000 people who die are candidates for organ donation, and thats if their families agree to donation.

Even if you register as a donor, it is still up to your family to make the final decision.

Making your family aware that you want to be a donor is the most important thing you can do. For more information visit http://www.donatelife.net or http://www.Organize.org.

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Giving the Gift of Life ~ National Donor Day - Shoshone News Press

Bone Marrow Stem Cells Comments Off on Giving the Gift of Life ~ National Donor Day – Shoshone News Press | February 20th, 2017

A MAN who narrowly missed out on a heart transplant has become the first patient in Europe to receive a revolutionary new treatment on compassionate grounds.

Gordon Foster, 59, suffered the first of a number of heart attacks at 30, and was advised he would need a heart transplant.

But as his heart functionality was working at 17 per cent, he was not eligible for the transplant which requires functionality at below 16 per cent.

Gordon, a welder, was then made redundant and became depressed.

His poor health meant he became housebound and, at times, was unable to move from one room to the next.

But his life has now been transformed as he has become the first patient in Europe to undergo stem cell treatment to regenerate part of his heart muscle through the new Compassionate Treatment Programme at St Bartholomews Hospital in London.

The treatment meant Gordon was given injections to stimulate the growth of his own stem cells. Bone marrow was then taken and the stem cells extracted from it before being injected back into his heart to regenerate the muscle.

Within a week of the operation, Gordon no longer needed to use his stair lift, his daily tasks such as walking up the stairs and doing housework became easier and he was able to enjoy spending time with his wife and children.

Gordon, who lives in Bridlington, said: I will forever be thankful to the Heart Cells Foundation, and the work of the team at St Bartholomews Hospital, as without them I believe I wouldnt be here today and Im enjoying every moment I spend with my wife and children.

Not only has the stem cell treatment I received helped to improve my physical health, but it has also massively improved my mental health and I now live every day with hope for the future.

Professor Anthony Mathur, consultant at St Bartholomews Hospital, said: Gordons story proves just how important it is to offer cell therapy to those who have no other medical choice.

With more than a million people suffering with heart disease and failure in the UK, the need for treatment in this field has never been greater.

We hope to lead the way to the treatment ultimately being available to thousands of other patients through the NHS, so we can help people like Gordon to lead near normal lives again.

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New start for stem cell heart op man, Gordon - The Press, York

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Slacking off in ALS? Mutant SOD1 may partially close the SLACK ion channel resulting in increased excitability in some neurons (Zhang et al., 2017).[Image: NIGMS.]

Increased activity in the motor cortex of the brain may occur in most forms of ALS (see September 2015 news). But whether this hyperexcitability contributes to the disease remains an open question.

Now, researchers at Yale University make the case that ALS-linked mutant SOD1 may downregulate a key sodium-gated potassium ion channel, known as SLACK, through an apoptosis signal-regulatingkinase1 (ASK1)-based mechanism (Zhang et al., 2017).

The findings may help explain how motor neuron hyperexcitability occurs in ALS. These changes in excitability may contribute to disease pathogenesis and may underlie fasciculations, one of the earliest clinical manifestations of the disease.

The question is whether this pathway is the primary way that SOD1 mutations cause disease, said Steve Vucic of the University of Sydney, who was not involved in the study. If so, [there] is a tremendous opportunity for developing treatments against these kinase pathways.

The study is published on January 24 in the Journal of Neuroscience.

Excitement builds

Neuronal hyperexcitability emerged in recent years as an early and potentially unifying stepin ALS, due to its detection in a number of sporadic and genetic forms. While the evidence is still not yet conclusive, some studies suggest that this prolonged excitation can lead to toxicity, strengthening the case that these changes in excitability may contribute to the disease (Fritz et al., 2013; Hadzipasic et al., 2014).

How hyperexcitability occurs in ALS remains unclear. But a growing number of studies suggest that mutant SOD1 may be involved, at least in some cases of the disease (Wainger et al., 2014; van Zundert et al., 2008).

Researchers at Yale University, led by Leonard Kaczmarek and Arthur Horwich, wondered whether mutant SOD1 could trigger hyperexcitability in motor neurons by downregulating a key membrane-bound ion channel called SLACK (sequence like a calcium-activated K channel), also known as KCNT1 or KNa1.1.

SLACK is a key regulator of excitability that helps neuronsreturn to the resting state upon firing. Its widely expressed in the CNS and its dysfunction has also been implicated in neurological diseases including Fragile X and epilepsy (Barcia et al., 2012; Heron et al., 2012; Martin et al., 2014).

Hyperexcitability in the bag. Researchers use sea slug bag cell neurons to study underlying hyperexcitability mechanisms. [Image: Kabir et al., 2001 under a CC-BY-NC-SA license.]

To investigate this question, first co-authors Yalan Zhang and Weiming Ni turned to the neuronalmodel system, the sea slug Aplysia. The system gained recognition in the 1960s for its role in providing Eric Kandel Nobel Prize-winning insights into learning and memory formation.

The approachinvolves the manipulation and study of bag cell neurons, very large neuroendocrine cells in the sea slugs abdomen that control egg laying. The really big advantage is that, because of their size, you can inject materials into them and then use a very fine microelectrode to record changes in excitability, all without any disturbance of the cytoplasm, Kaczmarek said.

The researchers compared the activity of potassium channels in bag cell neurons in the presence or absence of wild-type or mutant SOD1, including soluble oligomers of increasing size. They found that SOD1 or mutant SOD1 G85R monomers had no effect. But when they injected SOD1 G85R oligomers, they observed a reduction in outward potassium currents by 20-30%. This drop occured within 10 minutes and increased with larger oligomer size.

Whats more, SOD1 G85R oligomers increased excitability of these neurons. Injection of these soluble 300 kDa protein complexes decreased the neurons resting membrane potential and increased its susceptibility to firing in response to applied stimuli, they found.

Further experiments identified the SLACK channel as the one most likely to have been affected by mutant SOD1, because neurons pretreated with siRNA against SLACK mitigated the effect of these protein complexes in these neurons.

Together, the results suggest that soluble mutant SOD1 oligomericcomplexes may lead to hyperexcitability due to partial closure of SLACK, a key sodium-gated potassium channel that helps neurons return to their resting state upon firing.

ASK1ing for trouble

How could mutant SOD1 downregulateSLACK? The researchers suspected that these effects may be triggered by ASK1, a key kinase that has been previously implicated in the destruction of motor neurons in the disease (Raoul et al., 2002).

ASK1 has been shown to mediate key effects of mutant SOD1 in mouse models of the disease including ER stress and disruption of axonal transport (Lee et al., 2016; Song et al., 2013). In addition, inhibitingthis pathway appears to extend the survival of a SOD1 G93A mouse model of the disease (Fujisawa, et al. 2016).

To investigate this possibility, the researchers blocked ASK1 signaling and determined the impact of SOD1 oligomeric complexes on potassium channel activity. They found that the suppression of outward potassium current could be abolished by pre-treatment with an inhibitor of the apoptosis signaling regulating kinase ASK1. Similar effects were achieved with an inhibitor of one of ASK1s downstream targets, JNK.

The results, Kaczmarek said, suggest that mutant SOD1 oligomericcomplexessuppressSLACK channels in neurons through a ASK1-based mechanism, causing hyperexcitability.

Its an attractive idea, says Massachusetts General Hospitals Brian Wainger, who was not involved in the study. The findings may provide a potentially direct mechanistic connection between mutant SOD1 and motor neuron hyperexcitability in ALS.

Mind your Potassium and KCNQs. Researchers are evaluating Kv 7.2 potassium channel activators including retigabine (orange) in hopes to reduce hyperexcitability in people with the disease. More specific channel modulators are being developed. One such activator, AUT00063, is being evaluated at the phase 2a stage by the London startup Autifony Therapeutics to treat hearing disorders. [Miceli et al., 2011 under CC BY 4.0 license.]

But a change in excitability may not be the only or even the most important consequence of SLACK down regulation, according to Kaczmarek. SLACK may act as an activity sensor, providing a direct link between neuronal firing and protein synthesis.

His teamhas previously shown that SLACK channel activity plays a role in synaptic development, through its ability to regulateactivity-dependent protein synthesis (Brown et al., 2010; Zhang et al., 2012). When you precipitate the channel from mammalian brain, it pulls down several messenger RNAs, he pointed out, and mutations that cause channel overactivity are associated with epilepsy (Barcia et al., 2012; Kim et al., 2015).

In fact, Kaczmarek added, it may not be the hyperexcitability of motor neurons that is toxic in ALS, but rather its proposed (but not yet tested) consequences on protein synthesis. A rapid change in the activity of these channels, as we saw here, is likely going to alter protein synthesis, and that can produce much longer-lasting effects, potentially more consistent with a late-onset disease.

This was an extremely elegant study, and an ingenious way to approach the issue of hyperexcitability, said Steve Vucic, who, in collaboration with University of Sydneys Matthew Kiernan in Australia helped identify these neuronal changes as an early sign of ALS in people with the disease. The goal now will be to see if this same pathway is affected in the mammalian models, or in human ALS iPS cells.

Brian Wainger agrees. The key questions, according to Wainger, are whether these findings hold up in mammalian models, and whether these findings can be generalized to other forms of the disease.

Searching for ALS-linked gene variants in SLACK or related ion channels might also provide insight into its relevance for the human disease, added Vucic.

Approaching the clinic

Hyperexcitability is clearly a clinical feature of many forms of familial and sporadic ALS, explains Wainger. Thats why it is attractive as a convergent mechanism for many forms of ALS. But one of the challenges is to determine to what extent an increase in firing is relevant for disease pathogenesis, rather than, as some argue, being a compensatory mechanism. Directly modulating excitability is one of the clearest ways of answering that question directly, he added.

If motor neuron hyperexcitabilitydoes hold up as a driver of disease, however, it may be a good target for therapy, according to Kaczmarek. I see this as very much a therapeutic possibility.

The reason is because opening up these potassium ion channels may help motor neurons in people with ALS return to their resting state and thereby, reduce hyperexcitability in the disease.

Finding magneto. Researchers are using transcranial magnetic stimulation to evaluate in part whether mexiletine and retigabine reduce hyperexcitability in people with the disease.[Image: NIH].

Kaczmareks team is now hoping to do just that by developing a SLACK activator. The project is ongoing.

In the meantime, clinicians are aiming to reduce hyperexcitability in people with ALS by repurposing existing medicines in hopes to treat the disease. Brian Wainger is leading an effort to determine whether the epilepsy drug retigabine may be helpful in ALS. The drug, identified by Wainger as a potential treatment while in the laboratory of Kevin Eggan, may help normalize the activity of motor neurons by opening up Kv7 potassium channels in people with the disease (see April 2016 news; ; Wainger et al., 2014).

Across the US, the University of Washingtons Michael Weiss is taking a different approach. He is evaluating whether mexiletine, a sodium channel blocker, may reduce hyperexcitability in people with the disease (see March 2016 news). Both strategies are currently at the phase 2 stage.

In a disease that has a selective neuronal vulnerability like ALS, says Wainger, I think it is likely that the electrophysiological properties of the neuron are going to be related to the degenerative nature of the disease. So normalizing those properties may have a good chance of being helpful.

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Brown MR, Kronengold J, Gazula VR, Chen Y, Strumbos JG, Sigworth FJ, Navaratnam D, Kaczmarek LK. Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack. Nat Neurosci. 2010 Jul;13(7):819-21. [PubMed].

Zhang Y, Brown MR, Hyland C, Chen Y, Kronengold J, Fleming MR, Kohn AB, Moroz LL, Kaczmarek LK. Regulation of neuronal excitability by interaction of fragile X mental retardation protein with slack potassium channels. J Neurosci. 2012 Oct 31;32(44):15318-27. [PubMed].

Kim GE, Kronengold J, Barcia G, Quraishi IH, Martin HC, Blair E, Taylor JC, Dulac O, Colleaux L, Nabbout R, Kaczmarek LK. Human slack potassium channel mutations increase positive cooperativity between individual channels. Cell Rep. 2014 Dec 11;9(5):1661-72. [PubMed].

disease-als hyperexcitability mexiletine retigabine SOD1 topic-preclinical topic-researchmodels

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A key ion channel may SLACK off in ALS - ALS Research Forum

IPS Cell Therapy Comments Off on A key ion channel may SLACK off in ALS – ALS Research Forum | February 20th, 2017

VAIL Hallways at the world-famous Steadman Clinic are lined with framed, autographed jerseys of star athletes who have had surgery here, including John Elway, Mario Lemieux and Alex Rodriguez.

The clinic and its associated Steadman Philippon Research Institute (SPRI) attract world-class talent from all fields including U2 drummer Larry Mullen Jr., who joined the institutes board after he was a patient here but perhaps its top recruit was a renowned scientist researching ways to help injuries heal faster and slow down the way our bodies age.

Were trying to develop the iPhone 9 of medicine, said Dr. Johnny Huard, chief scientific officer and director of the institutes Center for Regenerative Sports Medicine. Your iPhone 6 and 7 are great, its doing everything you want, but youre looking on the web at what the iPhone 8s going to do. We want to have surgeons here doing surgery on our best football, hockey, basketball players, and instead of losing a year to heal, can we heal them in six months? Three months? Would that be great?

Joe Amon, The Denver Post

The field is called biologics, and its transforming orthopedics by using cells that heal produced in the patients body in concentrated injections that can hasten tissue repair directly at the site of the injury. Huard is leading cutting-edge research into stem cells and platelet-rich plasma (PRP) therapy that he believes will some day delay age-related diseases and cut the recovery time from serious injuries, such as to the knee, in half.

Stem cells are undifferentiated cells that can become specialized cells muscle, bone, cartilage to help repair tissue. Platelets carry proteins that help in the healing process. The breakthroughs Huard and his colleagues are pursuing hold exciting promise for weekend warriors as well as for star athletes.

I dont think we can reverse aging, but I think we can age better and recover from injury better, said Dr. Marc Philippon, managing partner of the Steadman Clinic and co-chairman of the research institute. As a surgeon my biggest challenge is, if I cut on you theres always that healing phase. We want to recover faster. But the most important thing is prevention of injury. If your cells are aging better, youll have less injury. The way I look at it, thats going to put us out of business, but thats OK. Its a good way to go out of business.

A world-class scientist, Huard discovered muscle-derived stem cells in 1998. Before joining SPRI two years ago he was the director of the Stem Cell Research Center at the University of Pittsburgh.Researchers here believe injections of stem cells and PRP can help delay or prevent the need for joint replacements, and at the adjacent clinic they can test their theories in clinical trials. They have shown in animal studies that young stem cells can rejuvenate old stem cells.

To that end Huard advocates passionately that when a child is born, stem cells from the umbilical cord should be harvested and frozen at minus-80 degrees Fahrenheit. As bodies age, stem cells diminish in number and vitality, but they can be preserved in suspended animation while frozen. Those cells later can be thawed and reintroduced into the body as younger and more robust stem cells than the ones that have aged in the patient, performing like a fountain of youth.

Thats the best gift you can give to that baby, said Huard, a French Canadian with a playful wit. Its the best gift you can give to that mother, too, because that (umbilical cord) is part of her, too. Its not only part of the baby. Can you believe the impact of that?

Stem cells, aging and exercise

Because stem cells can develop into every cell type in the body, researchers believe they can be used to hasten repair of nerves, bone and muscle. Bone marrow transplants are the most common form of stem cell therapy currently in use, but stem cells may be useful in fighting neurodegenerative diseases and other conditions.

We can use them to repair bone, cartilage, the heart, the bladder, Huard said. We have clinical trials now ongoing for bladder and the heart.

Imagine a Broncos running back blowing out his anterior cruciate ligament in training camp but being able to return to the field during the regular season. Huardforesees that day, as well as a time when patients whose stem cells were harvested and stored at birth will be able to have them injected into their knees decades later after ACL repair, for example, which theoretically could allow the person to recover much faster.

If I harvest stem cells from your muscle today, lets say I find 100 stem cells, but if I do the same thing 30 years ago I may have gotten 10,000, Huard said. Not only that, but the 100 stem cells you have are tired. They have been dividing and trying to repair your muscle.

When one of Huards children was born 17 years ago and it came time for Huard to cut the umbilical cord, he asked the nurse what they were going to do with it.

My wife said, Can you stop being a scientist and be my husband for a minute here? Huard tells the story with amusement, but he is passionate that umbilical cord stem cells should be saved.

I tell people, No more flowers, just freeze the stem cells from that newborn, Huard said. Thats the best gift you can give to that kid.

In the meantime, Huard believes exercise remains the best anti-aging mitigation we have. Beyond the benefits already well known, he is convinced exercise increases the production of stem cells and delays the aging process.Researchers found that mice that run on treadmills heal significantly faster than sedentary mice. Mice who exercised also had a better survival rate after being injected with cancer cells than those that were sedentary.

Huardbelieves exercise helps the brain as well as the heart in ways that might not be fully understood but might have implications for the prevention or delay of dementia and Alzheimers.

Stem cells come from blood vessels, Huard said. What can we do to increase the number of blood vessels? If we can do that, then we can probably improve tissue repair. If you exercise, you increase the number of blood vessels in your tissues.

Platelet-rich plasma therapy

PRP therapy is already in widespread use, not just in elite athletes but in recreational athletes as well. Sometimes it works well, and sometimes it doesnt work at all. Huard is trying to find out why.

Platelets in the blood carry proteins called growth factors that help the body repair injured tissue. In PRP therapy, a patients blood is removed and spun in an centrifuge or filtered to separate platelets. Then the platelet-rich plasma is injected into the site of an injury with hopes of speeding the healing process.

When you injure something, you bleed, Philippon said in his office with a view of Vails ski trails. Some of the first elements going there are your platelets, and theres a reason for that. Platelets have the growth factors, also what we call the chemotactic factors, to attract whats needed (to heal).

Philippon has used PRP to hasten healing of hip tendons in football players, for example.

What we found was that those I injected with PRP early recovered faster, Philippon said. We have that data here. We know, for a tendon injury, PRP is a great therapy.

Huard had elbow surgery last year after snapping a tendon off the bone in a ski accident I like to go fast, he said with a grin and Steadman surgeon Peter Millett asked Huard if he wanted a PRP injection in hopes of hastening recovery.

I said, Of course! You know what? I never wore a sling, Huard said. The week after, I was running. Three weeks after, I was back skiing.

But did the PRP help?

I dont know, Huard said.

So Huard is studying the success rate of PRP therapy in patients who receive it after surgery at the Steadman Clinic. When Philippon uses PRP on a patient, for example, he will set aside a fraction of that PRP and give it to Huard to analyze in the lab. Huard will catalog the different growth factors in each sample and then wait to see how the patients respond.

After this Im going to go back to Marc and say: Which patient worked? Which one was your best patient? Huard said. If he tells me patient No. 24 and 32 and 48, Im going to go back and try to see what those three patients PRP had in common in terms of growth factors.

Then Huard will be able to better advise surgeons before using PRP.

Lets say we find when IGF1 (insulin growth factor one) is high in your blood, PRP always works, Huard said. You know what Im going to give to those surgeons? Im going to say, Before you give PRP, take a blood draw, we go in the lab, test for IGF1, and if IGF1 is high, 95 percent chance PRP is going to help. But another patient, if IGF1 is not high, Based on our tests, I dont think PRP is going to help.

Another thing we found in PRP, it is a mixed bag. You have good things in PRP but you have bad things, too. So were doing science where Im going to take PRP, Im going to take out the bad guys.

As with stem cells, Huard foresees a day when a young patients PRP can be frozen and used decades later to delay aging, administered in conjunction with stem cell injections to work in synergy.

I think the two can be combined somehow, Huard said. They are different, but the stem-cell therapy and the PRP somehow can be together. If I have your PRP from 20 years ago and I have your stem cells from 20 years ago, I can make a very nice mixture, inject this into you. Sometimes adding one thing to another, biologically, it equals not two but three.

Having his laboratory in the same building as the Steadman Clinic, which has eight surgeons on staff, is a boon for Huard in his research. He takes ideas to them and vice versa.

I dont do science just to do science, he said. I do science to improve quality of life, and I think I can make a major contribution in the field. If you delay aging by 10 years, you delay all those age-related disorders by 10 years. The implications for health care is amazing.

Biologics: Using tools produced by a patients body such as stem cells and platelet-rich plasma (PRP) to help the patient heal faster and better.

Regenerative medicine: This and tissue engineering are promising treatment approaches that can enhance or promote musculoskeletal tissue healing and regeneration following surgery or injection therapy. Biological treatments such as growth factor supplementation, PRP and bone marrow concentrate have been shown to improve patient function and quality of life.

Platelet-rich plasma: A biologic treatment that is produced by concentrating the patients own blood to yield a high platelet count. Platelets are important blood components that secrete hundreds to thousands of biological factors that initiate musculoskeletal tissue healing and regeneration.

Stem cells: Stem cells have the ability to transform into specific musculoskeletal tissue cells. These types of cells also secrete biological factors that initiate musculoskeletal tissue healing and regeneration. There are several forms of stem cells, such as muscle-derived stem cells, bone marrow-derived stem cells, adipose-derived stem cells and others.

John Meyer, The Denver Post

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Researchers in Germany have discovered that a tumor suppressor protein thought to prevent acute myeloid leukemia (AML) can actually promote a particularly deadly form of the disease. The study, "RUNX1 cooperates with FLT3-ITD to induce leukemia," which will be published online February 17 in The Journal of Experimental Medicine, suggests that targeting this protein could be an effective treatment for certain AML patients.

AML accounts for over 1 percent of all cancer deaths in the United States and is characterized by an excessive proliferation of hematopoietic stem cells in the bone marrow and their subsequent failure to differentiate into white blood cells. AML can be caused by various combinations of gene mutations. One of the most common mutations is in the gene encoding the cell surface signaling protein FLT3, and patients with this mutation show poor rates of survival. The mutant form of FLT3 can promote cell proliferation, but experiments in mice have shown that it isn't sufficient to block white blood cell differentiation and induce AML on its own.

Carol Stocking and colleagues at the Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology in Hamburg noticed that many patients carrying the mutant form of FLT3 also showed increased levels of a transcription factor called RUNX1. "This was unexpected because up to 20 percent of AML patients carry mutations that inactivate RUNX1, which is generally considered to be a tumor suppressor that prevents the formation of leukemias," Stocking says.

Stocking's team found that reducing RUNX1 levels attenuated the ability of human AML cells expressing mutant FLT3 to form tumors when injected into mice. In contrast, elevated RUNX1 levels worked with mutant FLT3 to induce AML. Mouse hematopoietic stem cells expressing mutant FLT3 were highly proliferative, and co-expression of RUNX1 blocked their differentiation, allowing them to give rise to AML.

Mutant FLT3 appears to stabilize and activate RUNX1 by promoting the transcription factor's phosphorylation. Active RUNX1 then blocks white blood cell differentiation, at least in part, by inducing another transcription factor called Hhex. Hematopoietic stem cells expressing both Hhex and mutant FLT3 also gave rise to AML, the researchers found.

RUNX1 may therefore suppress the initiation of AML but, after being activated by mutant FLT3, block white blood cell differentiation and promote tumor development. "Therapies that can reverse this differentiation block may offer significant therapeutic efficacy in AML patients with FLT3 mutations," says Stocking. "Ablating RUNX1 is toxic to leukemic cells but not to normal hematopoietic stem cells, so inhibiting RUNX1 may be a promising target in combination with FLT3 inhibitors."

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Tumor suppressor promotes some acute myeloid leukemias, study reveals - Science Daily

Bone Marrow Stem Cells Comments Off on Tumor suppressor promotes some acute myeloid leukemias, study reveals – Science Daily | February 19th, 2017

Asterias Biotherapeutics (AST) continues to generate excitement and buzz around its stem cell treatment for catastrophic spinal cord injury (SCI). I wrote about this historic event back in September. Thats when the company first released results about this transformative medical breakthrough.

Asterias has now released follow-up data. This was gathered at six and nine months after six quadriplegics received treatment. All six continue to show improvement in motor function and sensation. This is truly wonderful news for those with SCI.

There are also broader medical implications and these should be of great interest to investors.

The difference between this stem cell therapy and traditional drug therapies is huge. Drug therapies have specific and mechanistic impacts. But stem cells derived from embryonic cells work a different way. They draw on the massive DNA databanks in their nuclei. They then use these genetic programs to interact with their surroundings and repair damaged structures.

The Asterias oligodendrocyte progenitor cells were derived from a single unused embryo (from an IVF procedure in the late 1990s). Such embryos are often discarded. But this one was donated to create an unlimited number of therapeutic cells. Both the Bush and Obama Administrations approved the cell line.

When injected into the site of a spinal cord injury, these cells create healthy new spinal cord structures. They restore myelin sheaths (which are like an insulating material on nerves) and repair the lesions caused by injury. They send chemical signals that stimulate the growth of nerve cells. They also generate blood vessels that deliver oxygen and nutrients (and clear out toxic substances).

In works of science fiction, you may have read about nanobots. These are theoretical nanomachines that can fix profound biological damage. But the truth is that we all have this type of device in our bodies at the embryonic stage of development. Each uses the complex repair systems that can be found in the human genome.

These are the cells (AST-OPC1) that were given to patients in the SCI trial. The result is that patients who could not breathe on their own can now perform complex physical tasks. We have seen them lift weights, text, and type 35 words a minute and they continue to improve.

Most people assume this therapy must be the most modern of biotechnologies. In truth, its quite old in modern scientific terms. Dr. Michael West oversaw the creation of this therapy over two decades ago as Gerons chief science officer.

When that company stumbled, he brought the clinical trial and Gerons IP into BioTime (*see disclosure below) as Asterias Biotherapeutics. When I spoke to Asterias CEO Steve Cartt, his excitement was palpable. Heres why.

Each year, about 17,000 people experience the kind of spinal cord injuries targeted by the current trial. AST-OPC1 would be the only approved treatment for this condition.

Cartt is now considering plans to extend clinical trials to those who have suffered less serious spinal cord injuries. This means the patient population for AST-OPC1 cells would expand a great deal.

These cells might also be used to treat other neurological diseases. Multiple sclerosis, for example, also involves the deterioration of the myelin nerve sheath. But this is just the tip of iceberg for pluripotent stem cell therapies. Many of our worst diseases can be addressed by these biological nanobots.

If spinal cords can be repaired, so can the connective tissue deterioration that leads to arthritis and joint failures. Im convinced we will see simple injections of stem cells to repair hip, knee, and other joints in the future.

BioTime has also done extensive research into stem cell therapies for heart muscle and cardiovascular repair. In fact, Dr. West has converted some of my cells to embryonic status. He then engineered them to become my heart muscle cells. There have been animal studies as well. The results indicate that these types of cells will repair the damage done by heart attacks.

Next up, though, is blindness. A BioTime subsidiary in Israel, Cell Cure Neurosciences, is in a phase 1/2a trial to treat dry age-related macular degeneration (dry-AMD). Israeli government grants have helped fund this project.

Based on animal trials, it seems that the companys retinal pigment epithelial cells will be successful in treating the leading cause of adult blindness. Dry-AMD is an attractive target because there is no effective treatment. From what Ive learned, I think that these cells will treat the wet form of macular degeneration and other causes of blindness as well.

This is the real importance of the Asterias SCI trial. Right now, were seeing the proof of concept for a biotechnology that will disrupt the entire healthcare market. I've written about this extensively in Tech Digest (subscribe here for free).

This change will happen sooner than you think. Japan has already revised its Pharmaceutical Affairs Act to speed up the approval of stem cell therapies. And on the home front, several of President Trump's candidates for FDA chief have endorsed similar reforms.

(*Disclosure: The editors or principals of Mauldin Economics have a position in BioTime (BTX) which has significant ownership of Asterias stock. They have no plans to sell their position at this time. There is an ethics policy in place that specifies subscribers must receive advance notice should the editors or principals intend to sell.)

This weekly newsletter by biotech expert Patrick Cox highlights research that is much more advanced than most people know, and the profit potential for investors is vast. Read about the latest breakthroughsfrom new, non-invasive cancer treatments to age-reversing nutraceuticals and vaccines that kill any virusas well as the innovative companies that work on them. Get Tech Digest free in your inbox every Monday.

DISCLOSURE: The views and opinions expressed in this article are those of the authors, and do not represent the views of equities.com. Readers should not consider statements made by the author as formal recommendations and should consult their financial advisor before making any investment decisions. To read our full disclosure, please go to: http://www.equities.com/disclaimer

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A Breakthrough in Stem Cell Treatment? - Equities.com

Spinal Cord Stem Cells Comments Off on A Breakthrough in Stem Cell Treatment? – Equities.com | February 18th, 2017

SOUTH SAN FRANCISCO, CA--(Marketwired - February 13, 2017) - VistaGen Therapeutics Inc. (VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, today reported financial results for the third quarter of fiscal 2017 ended December 31, 2016.

The Company also provided a corporate update, including anticipated milestones for AV-101, its new generation, orally available CNS prodrug candidate in Phase 2 development, initially for the adjunctive treatment of major depressive disorder (MDD) in patients with an inadequate response to standard antidepressant therapies approved by the U.S. Food and Drug Administration (FDA).

"We are excited about our progress during the last quarter, with several key advances related to our MDD-focused programs for AV-101, as well as potential regenerative medicine and drug rescue applications of our cardiac stem cell technology. Following productive discussions with the FDA last quarter, our team and key advisors have been working diligently to complete the diverse regulatory and technical activities necessary to support the planned launch of our Phase 2b study of AV-101 next quarter, a study we believe has game-changing potential for the millions of patients who battle MDD every day with inadequate therapies," commented Shawn Singh, Chief Executive Officer of VistaGen. "Also, our recent sublicense agreement with BlueRock Therapeutics was an important advance in our cardiac stem cell program while we remain primarily focused on our Phase 2 programs for AV-101. With potentially catalytic milestones in the coming quarters, we believe we are poised to unlock significant value for our shareholders throughout 2017," added Mr. Singh.

Recent Corporate Highlights:

The U.S. National Institute of Mental Health (NIMH) is currently conducting and fully funding a 20 to 25-patient Phase 2a study of AV-101 as a monotherapy for treatment-resistant MDD under VistaGen's Cooperative Research and Development Agreement (CRADA) with the NIMH (Phase 2a Study). Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH and a leading clinical expert on the use of ketamine for treatment-resistant MDD, is the Principal Investigator of the Phase 2a Study. Following recent guidance from the NIMH, the Company currently anticipates that the NIMH will complete the Phase 2a Study by the end of 2017.

VistaGen is preparing to launch a 280-patient, multi-center, double-blind, placebo controlled Phase 2b efficacy and safety study evaluating AV-101 as a new generation adjunctive treatment for MDD patients with an inadequate response to standard, FDA-approved antidepressant therapies. The Company currently anticipates commencing patient enrollment in the Phase 2b Study in the second quarter of 2017. Dr. Maurizio Fava of Harvard University Medical School will serve as the Principal Investigator of VistaGen's AV-101 Phase 2b Study. Topline clinical results from the Phase 2b Study are currently anticipated by the end of 2018.

Dr. Mark Smith, Chief Medical Officer of VistaGen, commented, "We look forward to starting patient enrollment in our Phase 2b study of AV-101 as an adjunctive therapy in the treatment of MDD. We believe we have significantly de-risked this Phase 2b study with a clinical trial methodology that is designed to overcome the challenge of placebo effects in psychiatric clinical trials. Based on the study protocol we have designed in collaboration with key opinion leaders in depression and neuroscience, including our Principal Investigator, Dr. Fava, we expect that achieving a successful outcome of our Phase 2b study will be integral in realizing AV-101's potential to displace atypical antipsychotics and non-drug interventions in the current depression treatment paradigm, representing a much needed treatment solution for physicians and patients, as well as an enormous opportunity for VistaGen."

Expected Near-Term Milestones:

"The NIMH recently updated us on their timelines for the completion of the Phase 2a study of AV-101 as a monotherapy for MDD. The Phase 2a study protocol requires considerable time and dedication from both the study participants and the multi-disciplinary NIMH teams involved. Patient enrollment for the Phase 2a study remains ongoing and we currently anticipate the NIMH's completion of the study by the end of 2017. Our top priority is to execute our plans for our Phase 2b study of AV-101 as a new generation adjunctive treatment of MDD, and we remain on track to launch that important study in the second quarter. As part of our Phase 2 program, this Phase 2b study has been specifically designed to achieve important outcomes that will be key to advancing AV-101 into a pivotal program in MDD and more broadly beyond MDD, as we continue to advance our global commercialization strategy. We are confident that our Phase 2 program is a major step forward in positioning AV-101 as a potentially transformative adjunctive treatment of MDD and other CNS disorders," concluded Mr. Singh.

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Summary of Financial Results for the Third Quarter of Fiscal 2017 Ended December 31, 2016

Revenue

The Company recognized $1.25 million in sublicense revenue pursuant to its cardiac stem cell technology sublicense agreement with BlueRock Therapeutics, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, in the third fiscal quarter ended December 31, 2016.

Research and Development Expenses

Research and development expense totaled $1.61 million for the third fiscal quarter ended December 31, 2016, compared to $806,300 for the quarter ended December 31, 2015, reflecting increasing focus on nonclinical and clinical development of AV-101 and preparations for launch of the AV-101 Phase 2b Study in the second quarter of 2017.

General and Administrative Expenses

General and administrative expense increased to $2.3 million in the third fiscal quarter ended December 31, 2016, from $1.3 million for the same period in the prior year. The increase in G&A expense is the result of increased noncash stock compensation expense attributable to option and warrant grants in the period to employees, independent members of the Company's Board of Directors and consultants and other noncash expense related to grants of equity securities in payment of certain professional services, and a combination of corporate expenses, including investor relations and corporate development initiatives.

Net Loss

For the third fiscal quarter ended December 31, 2016, the Company reported a net loss of approximately $2.6 million, or a net loss attributable to common stockholders of $0.34 per common share, compared to a net loss of approximately $2.1 million, or a net loss attributable to common stockholders of $1.95 per common share for the same period in the prior year.

Cash and Cash Equivalents

As of December 31, 2016, the Company had approximately $5.6 million of cash, cash equivalents and short term receivables, including a $1.25 million short term sublicense fee receivable from BlueRock Therapeutics pursuant to the Company's December 2016 technology sublicense agreement with BlueRock Therapeutics. In January 2017, the Company received the $1.25 million sublicense fee payment from BlueRock Therapeutics and currently believes it has sufficient financial resources to fund its expected operations at least through the first half of 2017, including preparation for and launch of its planned AV-101 Phase 2b Study in MDD.

About VistaGen

VistaGen Therapeutics, Inc. (VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. VistaGen's lead CNS product candidate, AV-101, is a new generation oral antidepressant drug candidate in Phase 2 development. AV-101's mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat MDD, with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a Phase 2a monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH. VistaGen is preparing to launch a 280-patient Phase 2b study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressant therapies. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Phase 2b study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including chronic neuropathic pain, epilepsy, Parkinson's disease and Huntington's disease, where modulation of the NMDAR, AMPA pathway and/or key active metabolites of AV-101 may achieve therapeutic benefit.

VistaStem Therapeutics is VistaGen's wholly owned subsidiary focused on applying human pluripotent stem cell (hPSC) technology, internally and with third-party collaborators, to discover, rescue, develop and commercialize proprietary new chemical entities (NCEs), including small molecule NCEs with regenerative potential, for CNS and other diseases, and cellular therapies involving stem cell-derived blood, cartilage, heart and liver cells. In December 2016, VistaGen exclusively sublicensed to BlueRock Therapeutics LP, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, rights to certain proprietary technologies relating to the production of cardiac stem cells for the treatment of heart disease.

For more information, please visit http://www.vistagen.com and connect with VistaGen on Twitter, LinkedIn and Facebook.

Forward-Looking Statements

The statements in this press release that are not historical facts may constitute forward-looking statements that are based on current expectations and are subject to risks and uncertainties that could cause actual future results to differ materially from those expressed or implied by such statements. Those risks and uncertainties include, but are not limited to, risks related to the successful launch, continuation and results of the NIMH's Phase 2a (monotherapy) and/or the Company's planned Phase 2b (adjunctive therapy) clinical studies of AV-101 in MDD, and other CNS diseases and disorders, protection of its intellectual property, and the availability of substantial additional capital to support its operations, including the development activities described above. These and other risks and uncertainties are identified and described in more detail in VistaGen's filings with the Securities and Exchange Commission (SEC). These filings are available on the SEC's website at http://www.sec.gov. VistaGen undertakes no obligation to publicly update or revise any forward-looking statements.

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VistaGen Therapeutics Reports Fiscal Third Quarter 2017 Financial ... - Yahoo Finance

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PTH regulates bone marrow progenitor fate Nature.com New research published in Cell Metabolism reveals an important mechanism underlying the anabolic effects of parathyroid hormone (PTH) on bone. Mice with conditional deletion of the gene encoding the PTH 1 receptor (PTH1R) in bone marrow progenitors ...

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PTH regulates bone marrow progenitor fate - Nature.com

Bone Marrow Stem Cells Comments Off on PTH regulates bone marrow progenitor fate – Nature.com | February 18th, 2017