Motor neurons are the nerve cells in the body responsible for controlling movement. A number of diseases are caused by damage to motor neurons, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). In order to treat these diseases, scientists are developing methods to generate new, healthy motor neurons from stem cells. A recent study has elucidated the cellular mechanisms that control the motor neuron differentiation, paving the way for new treatments for motor neuron diseases.

Each time we voluntarily move an arm or leg, or when our lungs involuntarily expand and contract, signals from the brain are sent along a chain to the spinal cord, where motor neuron cell bodies reside. These motor neurons terminate in muscle cells, where they transmit the nerve impulses in order to produce muscle contractions. In ALS, there is a progressive destruction of motor neurons due to either a genetic defect or an unknown environmental trigger. Motor neuron damage in ALS leads to progressive muscle weakness that affects all parts of the body, impairing the ability to speak, swallow, and eventually breathe. SMA is caused by gene mutations and is characterized by similarly progressive damage to motor neurons that causes muscle weakness. If respiratory muscles are affected, SMA can be fatal.

Scientists aim to develop gene therapies for these diseases that can repair the damaged motor neurons and improve the functioning and lifespan of patients. To do this, they must first understand the signals that induce motor neuron development from stem cells. Stem cells are the precursors for every type of cell in the body. They are triggered to differentiate into various cell types via cellular signaling molecules called transcription factors, which act on DNA to turn on specific genes. Which genes are turned on will determine the phenotypic fate of each cell. Typically, each cell goes through several stages of development before reaching its final fate.

A group of researchers from several universities recently teamed up to elucidate these programming pathways. They had previously discovered that a group of transcription factors called the NIL factors Ngn2, Isl1, and Lhx3 can induce motor neuron development from embryonic stem cells without passing through any of the intermediate stages. Moreover, the NIL factors achieved the transition to the motor neuron fate with a 90% success rate, and the process took only two days. This so-called direct programming pathway was an exciting finding with respect to clinical applications, because it can be achieved both in vitro and in living organisms at the site of cell damage.

In the current study published in the journal Cell Stem Cell, Esteban Mazzoni and colleagues further investigated the process by which transcription factors bind to and activate parts of DNA during the first 48 hours after NIL expression. First, the researchers used single-cell RNA sequencing (RNA-seq) to study the timing of gene expression after induction by NIL programming factors. RNA-seq is a technique that reveals the presence and quantity of RNA in a sample at a specific point in time. Thus, as transcription factors turn genes on, these genes are transcribed into RNA that can be measured and quantified.

The researchers also studied chromatin remodeling during motor neuron programming. Chromatin is a tightly-packed form of DNA which regulates the expression of genes through changes in its structure. Promoters are regions of the DNA where transcription factors bind in order to initiate gene transcription. Chromatin must undergo structural changes, called remodeling, in order for the DNA to be accessible to transcription factors. Typically, as cells move through the differentiation process, chromatin changes that occur at promoter regions will restrict the differentiation potential of the cell.

To study this chromatin remodeling process, a ChIP-seq time series was performed. ChIP-seq combines chromatin immunoprecipitation with DNA sequencing to identify the binding sites of proteins that associate with DNA. Antibodies against the bound proteins are used to extract protein-DNA complexes, and the DNA binding sites can be sequenced. In addition, the researchers used an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) to study chromatin accessibility. Proteins called transposons incorporate into exposed, or accessible, portions of chromatin. Therefore, identifying the locations of transposons in the DNA can indicate what parts of the DNA are being actively transcribed, or turned on.

This series of experiments revealed information about how genes are turned on and off over the 48-hour process of motor neuron formation. Initially, the transcription factors Ngn2 and Isl1/Lhx3 induce different sets of genes in parallel. Whereas Ngn2 controls genes associated with generic neuronal differentiation, Isl1 and Lhx3 activate genes specific for spinal cord and motor neurons. As programming progresses, Ngn2 induces the expression of two other transcription factors, Ebf and Onecut. These transcription factors modify the chromatin state to enable Isl1/Lhx3 binding to previously inaccessible sites on the DNA that contain the terminal motor neuron genes necessary to complete the programming process.

These experiments showed that the activities of Ngn2 and Isl1/Lhx3 act in tandem to induce direct motor neuron programming from stem cells. The researchers hope to apply these findings clinically. By triggering this programming pathway in the body, cells in the spinal cord can be induced to differentiate into motor neurons, replacing the neurons that are damaged in diseases such as ALS.

References

Czarzasta J., Habich A., Siwek T., Czaplinski A., Maksymowicz W., Wojtikiewicz J. (2017) Stem cells for ALS: an overview of possible therapeutic approaches. Int J Dev Neurosci. DOI: 10.1016/j.ijdevneu.2017.01.003

Farrar M., Park S., Vucic S., Carey K., Turner B., Gillingwater T., Swoboda K., Kiernan M. (2016) Emerging therapies and challenges in Spinal Muscular Atrophy. Ann Neurol. DOI: 10.1002/ana.24864

Mazzoni, E.O., Mahony, S., Closser, M., Morrison, C.A., Nedelec, S., Williams, D.J., An, D., Gifford, D.K., and Wichterle, H. (2013). Synergistic binding of tran- scription factors to cell-specific enhancers programs motor neuron identity. Nat. Neurosci. 16:12191227. DOI:10.1038/nn.3467

Velasco S., Ibrahim M., Kakumanu A., Garipler G., Aydin B., Al-Sayegh M., Hirsekorn A., Abdul-Rahman F., Satija R., Ohler U., Mahony S., Mazzoni, E. (2016) A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells. Cell Stem Cell. DOI: 10.1016/j.stem.2016.11.006

Image via ColiN00B / Pixabay.

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Home | Macau | Science | UM researchers develop new technology for stem cell storage

UM researchers have developed a new technology for cell storage and transport

The University of Macau (UM) Faculty of Health Sciences (FHS) has developed a technology that enables the storage of stem cells at room temperature for at least seven days without the loss of viability or biological activities. According to a statement issued by UM, this new technology does not rely on the traditional cryopreservation method which requires costly equipment and tedious cryopreservation procedures, thus enabling cell storage and transport under ambient conditions.

Under professor Ren-He Xus supervision, doctoral student Jiang Bin and postdoctoral researcher Yan Li, both from the FHS, engaged in the research study titled Spheroidal Formation Preserves Human Stem Cells for Prolonged Environment under Ambient Conditions for Facile Storage and Transportation. Together with the participation of Chris Wong Koon Ho, an assistant professor at the FHS, they successfully developed the new technology. The related paper has been published in Biomaterials, a renowned international journal in the field of biological materials.

The study found that preparing human mesenchymal stem cells (hMSC) to form spheroids with the hanging-drop or other methods, can reduce the cell metabolism and increase cell viability. Stored in a sealed vessel filled with regular culture medium, under ambient conditions without oxygen supply, the viability of hMSC in spheroids remained over 90 percent even after 11 days. This method is also applicable to higher pluripotent human embryonic stem cells.

Stem cells are found in various locations of the body such as bone marrow, blood, brain, spinal cord, skin, and corneal limbus. They are responsible for regenerating and repairing damaged tissues and organs in the body. Transplantation of stem cells can restore damaged tissues and organs to their original functions. For this reason, stem cells have significant clinical value. However, they require strict culturing and storage conditions. Extended exposure (over 24 to 48 hours) to unfavorable temperature, humidity, or levels of oxygen and carbon dioxide will cause the cells to gradually lose their functions and viability.

Currently, long-distance cell transport mainly relies on the costly method of cryopreservation. For short-distance transport, cells can be prepared in suspension or adherent culture, but the number of cells that can be transported via this method is limited. Moreover, cell viability decreases dramatically after transport for 48 hours under ambient conditions.

The UM claims that the new technology developed by its researchers can overcome the above limitations. With this technology, a sufficient dose of stem cells that are being transported can be used in patients without the need to freeze stem cells before transport and to thaw, revive, and proliferate the transported stem cells, a statement from the institution reads.

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Science | UM researchers develop new technology for stem cell storage - Macau Daily Times

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Macao Researchers Develop Room Temperature Storage Technology for Stem Cells

he University of Macao (UM) researchers developed a new way to store stem cells at room temperature for a minimum of 7 days without the loss of viability and biological activities, the universitys said in a press release Thursday.

UM said its researchers from Faculty of Health Sciences (FHS) has developed a technology which does not rely on the traditional cryopreservation method that requires costly equipment and tedious cryopreservation procedures, enabling cell storage and transport under ambient conditions.

Xu Renhe, a professor at the FHS of UM, has nearly two decades of research experiences in stem cells and their medical applications. He and his doctoral student Jiang Bin and postdoctoral researcher Yan Li, together with Dr. Chris Wong Koon Ho, an assistant professor at the FHS, engaged in the related research study titled Spheroidal Formation Preserves Human Stem Cells for Prolonged Environment under Ambient Conditions for Facile Storage and Transportation.

The related paper has been published in Biomaterials, a renowned international journal in the field of biological materials.

The study found that preparing human mesenchymal stem cells (hMSC) to form spheroids with the hanging-drop method or other methods can reduce the cell metabolism and increase the cell viability.

Stored in a sealed vessel filled with regular culture medium, under ambient conditions without oxygen supply, the viability of hMSC in spheroids remained over 90 percent even after 11 days. This method is also applicable to higher pluripotent human embryonic stem cells.

With this new technology, only regular culture tubes and media, which cost only several U.S. dollars, are required for storing and shipping probably any type of stem cells and non-stem cells that can aggregate, within a temperature range from 10 to 37C (centigrade).

Stem cells are found in various locations of the body such as bone marrow, blood, brain, spinal cord, skin, and corneal limbus. They are responsible for regenerating and repairing damaged tissues and organs in the body.

Have a terrific weekend.

cells, conditions, human, Macao, research, stem, storage, technology

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May 4, 2017 Neural stem cell therapies could eventually play a role in treating spinal cord injuries. Credit: woodoo007 / 123rf

Researchers in Qatar and Egypt, working with colleagues in Italy and the US, have found that injured spinal cords in rats show signs of tissue regeneration several weeks following injection with neural stem cells.

An estimated 2.5 million people worldwide live with spinal cord injury caused by various types of accidents and falls. "Much research is going into investigating the potential of stem cells in treating this and other neurological conditions," says Dr Hany Marei of Qatar University Biomedical Research Center.

The team isolated neural stem cells, which specifically differentiate into nerve tissue, from a structure in the front of the brain called the olfactory bulb. The olfactory bulbs were removed from human patients undergoing operations to extract brain tumours.

The team first genetically engineered the neural stem cells to carry a protein that causes them to fluoresce under the microscope. The researchers cultured the cells and demonstrated that they differentiated into a variety of nervous system cells.

They then injected the stem cells into rats whose spinal cords had been cut, and examined samples taken from the injured area regularly up until eight weeks after the injury. They compared these results with those of uninjured rats who did not receive injections, rats with injured cords that did not receive injections, and rats that underwent a sham operation in which the full procedure was done except for cutting of the spinal cord.

No signs of functional or tissue restoration were found in the control groups.

However, in the injured rats given neural stem cell injections, the team found that the stem cells differentiated into three types of nerve cells: oligodendrocytes and astrocyteswhich are involved in the production of the protective myelin sheath that surrounds nervesand neurons. There were no signs of immunorejection. However, there were also no signs of functional improvement in the rats in the form of movement of their hind limbs paralyzed by the injury.

The results indicate that injecting stem cells at sites of spinal cord injury can produce relatively normal neurons and other nervous tissue elements, but further studies are needed to promote locomotor recovery, says Marei. One possibility is that eight weeks (the upper limit in this study) is not enough time to restore damaged nerve tracts and neuronal circuitry.

Explore further: New hope for spinal cord injuries

Provided by: Qatar University

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CIRM California's stem cell research funding agency to lose ... San Francisco Business Times Randy Mills, who came in to right California's semi-public stem cell research funding agency, is leaving to head the National Marrow Donor Program. Mills three ... CA Stem Cell Agency Chief Randy Mills to Leave After Three Years ...Xconomy all 4 news articles »

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Remember stem cells? They were one of the biggest scientific controversies during the early years of George W. Bushs presidency.

At the time, scientists had realized thatembryonic stem cells had the incredible capacity to transform into virtually any cell in the human body and so could potentially lead to new treatments or cures for a multitude of illnesses. On the other hand, extracting these stem cells required destroying human embryos, an action opposed by some pro-life individuals.

EMBRYONIC stem-cell THERAPIES ARE GETTING TESTED IN ACTUAL PATIENTS

The stem-cell debate got really heated. But then ... it just sort of fizzled out from public view. So whatever happened to stem cells?

A couple of things helped lessen the controversy. By the late 2000s, researchers discovered other ways to createcells similar to embryonic stem cells without destroying human embryos, a promising advance that helped defuse the culture-war aspect. Then, in 2009, Obama somewhat loosened the Bush-era restrictions on federal funding for stem-cell research and thecompromise seemed to quiet both sides down a fair amount.

So, lately, scientists have been patiently continuing their stem-cell research in a less noisy atmosphere. And that work has actually led to a few advances like restoring some sight in 10 patients with vision diseases. But the stem-cell controversy is far from dead. Researchers still might need cells from embryos to create certain treatments. If it turns out that non-embryonic stem cells aren't good enough, that could re-ignite the culture wars. So here's a guide to the debate:

Shinya Yamanaka (right) receiving flowers from Sweden's ambassador to Japan in 2012, after it was announced that Yamanaka won a Nobel Prize in medicine. (Jiji Press/AFP/Getty Images)

Embryonic stem cells attracted scientific attention because they have the potential to grow into virtually any cell in the human body say, insulin-producing cells for people with diabetes, brain cells for people with Parkinsons, or even wholenew organs to replace faulty ones.

But for many people, there was one huge ethical problem: creating them required destroying an embryo. That's why, in 2001,George W. Bush decided to limit federal funding of research to a list of 60 pre-existing embryonic stem-cell lines (so as to discourage the destruction of any more embryos). Many scientists viewed the rules as too strict. Hence the controversy.

Obama SOMEWHAT relaxed Bushs restrictions on embryonic stem cells

But then in 2007, Japanese scientistShinya Yamanaka and his colleagues managed to coax cells from adult humans into embryo-like flexibility. In other words, they were able to create cells that seemed to resemble embryonic stem cells but that didn't require destroying an embryo. (These new cells were named induced pluripotent stem cells, IPSCs.) Other researchers began finding that adult stem cells have similar, but more limited, properties, too.

Meanwhile, the politics shifted. In 2009, Barack Obama came into office and signed anexecutive order that somewhat relaxed Bushs restrictions on embryonic stem cells. Under the new rules, the federal government would fund work on new stem-cell lines, but only if they had been made from leftover embryos from fertility clinics andwith non-federal money. That compromise seemed tohelp thecontroversy settledown.

A figure of visual ability after an embryonic-stem-cell-derived treatment (red line) in patients with macular degeneration over the course of 360 days. (Schwartz et al., The Lancet, October 15, 2014)

While the controversy has calmed down, stem-cell research is taking off and scientists are making advances with both embryonic and non-embryonic cells.

Much of the initial research on stem-cell therapies has focused on eye treatments. (That's because stem-cell therapies can be unpredictable and have sometimes lead to tumors in previous experiments. A tumor in an eye would be relatively easier to deal with and remove than tumors hidden deeper inside the body.)

In October 2014, researchers from the company Advanced Cell Technology (now called Ocata Therapeutics)showed that they had created new retina cells from embryonic stem cells for 18 patients who were going blind. Afterward, 10 of them had improved eyesight. Another group of researchers in Japan is trying to do the same thing with non-embryonic cells (those aforementioned IPSCs).

10 PEOPLE WHO WERE GOING BLIND HAD Improved eyesight AFTER EMBRYONIC STEM-CELL THERAPY

Other embryonic stem-cell research has focused on developing cells that can help treat spinal-cord injuries. A company called Geron startedsafety tests in such patients in 2010.

Although a few groups are continuing to work on embryonic stem cells, many are now focusing on non-embryonic stem cells like IPSCs because they're less contentious. "Everyone jumped very, very quickly on the IPS[C] bandwagon because it was eligible for federal funding, and then also any of the controversy [regarding embryos] was dropped," says Susan Solomon, CEO of the nonprofit New York Stem Cell Foundation.

But Solomon also thinks researchers have moved away from embryonic stem cells too quickly. "We felt that it was way too early to do that," she adds. Her organization still studies embryonic stem cells, among others in part because they may be able to do things that non-embryonic stem cells can't. It's just too early to tell.

It's important to note that despite all the overhype over the years, stem-cell science has been moving at the same slow pace as most scientific fields. There are still no FDA-approved treatments that use either embryonic stem cells or IPSCs. And that means that controversy over whether embryonic stem cells are needed for science and medicine is still unresolved.

(Shutterstock)

That said, the fight over stem cells hasn't gone away forever. And there's likely to be more conflict in the future.

Even after the Obama administration relaxed the rules on funding stem-cell research, there are still plenty of hurdles. For example, federal funding is currently prohibited for research on embryonic stem-cell lines made through a technique calledSCNT or cloning, which requires creating embryos in the lab.

This technique could one day prove useful because it can turn a person's own cells into a customized embryonic stem-cell line and would therefore stop people's immune systems from rejecting stem-cell treatments.

In 2013 and 2014, two groups published the firstdemonstrations of this technique with human cells. But all such research in the US must be done with private funds.

On top of all of this, some states directly ban some or all stem-cell research within their borders no matter who's paying for it:

Note: Minnesota has a vague law on the books that's currently interpreted to mean that embryonic stem-cell research is ok. Missouri's law is a bit self-conflicting. For more details, check out The Hinxton Group's site, which includes quotations from the relevant regulations themselves.

"We went from more of a legislative vacuum to our current patchwork quilt, with legislation enacted in all of the jurisdictions where interest groups had enough clout to get the job done," Alan Regenberg, Director of Outreach and Research Support at the Johns Hopkins Berman Institute of Bioethics, told me in an email.

Several things could bring the stem-cell fight back. For example, a clinical trial could come out with some really impressive results on some sort of stem-cell treatment renewing the debate over whether regulations should be loosened. Conversely, a social conservative could run for president and bring up the ethical issues on the campaign trail. And no matter who lands in the White House in 2016, its reasonable to expect some major changes in federal policy and fast. Both George W. Bush and Barack Obama implemented their rules within the first year in office.

In 2013, Obama's stem-cell policy survived Supreme Court case Sherley v. Sebelius.

A piece on the first embryonic stem-cellmedical trials in people, by Sarah Boseley at the Guardian

Update: Clarified the current interpretation of Minnesota's stem cell laws and changed the map to match.

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April 28, 2017 Neurons (red) and muscle cells (green) produced from NMPs in the laboratory. Credit: James Briscoe, Francis Crick Institute

A study from scientists at the Francis Crick Institute, the Max-Delbrck Center for Molecular Medicine, Berlin and the University of Edinburgh sheds new light on the cells that form spinal cord, muscle and bone tissue in mammalian embryos.

This discovery paves the way for generating these tissues from stem cells in the laboratory and could lead to new ways of studying degenerative conditions such as motor neuron disease and muscular dystrophy.

In embryos, the spinal cord, muscle and skeleton are produced from a group of cells called NMPs (neuro-mesodermal progenitors). These cells are few in number and exist only for a short time in embryos, despite giving rise to many tissues in the body. Their scarcity and inaccessibility has made studying NMPs challenging. Now, by using the latest molecular techniques, the research team has for the first time deciphered gene activity in NMPs. They used an advanced technique called single-cell transcriptional profiling, which analyses individual cells to provide a detailed picture of gene activity in every cell.

The technique allowed the team to establish a molecular signature of NMPs and to show that NMPs produced from stem cells in petri dishes in the laboratory closely resemble those found in embryos. This enabled the team to use lab-grown NMPs to learn more about these cells and how they make spinal cord, muscle and bone tissue. By manipulating the cells in petri dishes and testing the function of specific genes, the researchers re-constructed the regulatory mechanism and formulated a mathematical model that explains how NMPs produce the appropriate amounts of spinal cord and musculoskeletal cells.

Dr James Briscoe, who led the research from the Francis Crick Institute said:

"For embryonic development to progress smoothly, NMPs must make the right types of cells, in the right numbers at the right time. Understanding how cells such as NMPs make decisions is therefore central to understanding embryonic development. Single cell profiling techniques, including the ones we used in this study, are giving us unprecedented insight into this problem and offering a new and fascinating view of how embryos produce the different tissues that make up adults."

First author of the study Dr Mina Gouti, from the Max-Delbrck Center for Molecular Medicine, Berlin said:

"Improving our understanding of NMPs doesn't only answer an important developmental biology question but also holds great promise for regenerative medicine. It takes us a step closer to being able to use tissue from patients with diseases that affect muscles and motor neurons in order to study the causes and progress of these diseases. Being able to grow cells in the laboratory that faithfully resemble those found in the body is crucial for this."

The paper, A gene regulatory network balances neural and mesoderm specification during vertebrate trunk development, is published in Developmental Cell.

Explore further: Researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

More information: Mina Gouti et al. A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development, Developmental Cell (2017). DOI: 10.1016/j.devcel.2017.04.002

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Cedars-Sinai scientists are seeking to build an improved stem-cell model of amyotrophic lateral sclerosis (ALS) to accelerate progress toward a cure for the devastating neurological disorder. Their findings demonstrate that ...

esearchers from Hokkaido University in Japan together with an international team of scientists implanted specialized embryonic stem cells into the severed spinal cords of rats. The stem cells, called neural progenitor cells, ...

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A study from scientists at the Francis Crick Institute, the Max-Delbrck Center for Molecular Medicine, Berlin and the University of Edinburgh sheds new light on the cells that form spinal cord, muscle and bone tissue in ...

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A quick glance at your calendar will reveal that we're now in 2017. 2017, you may recall, is the year when contraversial surgeon Sergio Canavero has promised to perform the world's first human head transplant.

But just how feasible is a human head transplant? Is it the stuff of science fiction, or does it have a basis in current sceintific thinking? Read on for everything you need to know about 2017 most alarming scientific development.

A human head transplant is exactly what it sounds like taking one living head and putting it onto a new body.

But actually, thats a little misleading. In real terms, its a body transplant, as the head will be gaining a new body to control. However, as the term whole body transplant is already used to mean transferring the brain between bodies, calling it a head transplant makes it clear that the whole head is to be switched, brain included.

Until recently, a head transplant seemed totally implausible, but the Italian scientist Dr Sergio Canavero believes its possible, and intends to conduct the first surgery in 2017.

Canavero outlines the procedure in detail here, but these are the basics of the process. Remember: dont try this at home, kids.

The donor body and the head to be attached are first cooled down to 12-15C to ensure that the cells last longer than a few minutes without oxygen. The tissue around the neck is then cut, with the major blood vessels linked with tiny tubes. The spinal cord on each party is then severed cleanly with an extremely sharp blade.

"Post coma, Canavero believes the patient would immediately be able to move, feel their face and even speak with the same voice."

At this point, the head is ready to be moved, and the two ends of the spinal cord are fused using a chemical called polyethylene glycol, encouraging the cells to mesh. This chemical has been shown to prompt the growth of spinal cord nerves in animals, although Canavero suggests that introducing stem cells or olfactory ensheathing cells into the spinal cord could also be tried.

After the muscles and blood supply are successfully connected, the patient is kept in a coma for a month to limit movement of the newly fused neck, while electrodes stimulate the spinal cord to strengthen its new connections.

Following the coma, Canavero anticipates that the patient would immediately be able to move, feel their face and even speak with the same voice. He believes physiotherapy would allow the patient to walk within a year.

He explains his suggested methods in the TED talk below.

Sceptical would be a nice way of putting it. Horrified would, in most cases, be more accurate.

Dr Hunt Batjer has attracted headlines for being particularly blunt: I would not wish this on anyone. I would not allow anyone to do it to me as there are a lot of things worse than death.

Dr Jerry Silver witnessed the 1970s monkey head transplant experiment more on which later and describes the procedure as bad science, adding that just to do the experiments is unethical. This is a particular blow to Canavero, as he states that Silvers own work in reconnecting rats spinal cords should give hope to the human head transplant. Silver dismisses this: To sever a head and even contemplate the possibility of gluing axons back properly across the lesion to their neighbours is pure and utter fantasy in my opinion.

Dr Chad Gordon, professor of plastic and reconstructive surgery and neurological surgery at Johns Hopkins University, agrees that Canaveros claims are scientifically implausible. He told BuzzFeed: Theres no way hes going to hook up somebodys brain to someones spinal cord and have them be functional.

On the conservative side, were about 100 years away from being able to figure this out, he continued. If hes saying two, and hes promising a living, breathing, talking, moving human being? Hes lying.

Dr Paul Myers, associate professor of biology at the University of Minnesota at Morris, puts it even more explicitly: This procedure will not work... Try it with monkeys first. But he cant: the result would be, at best, a shambling horror, an animal driven mad with pain and terror, crippled and whimpering, and a poor advertisement for his experiment. And most likely what hed have is a collection of corpses that suffered briefly before expiring.

Others wonder whether Canavero might simply be enjoying the limelight with a PR stunt, including Dr Arthur Caplan, director of ethics at the NYU Langone Medical Centre. Describing the doctor as nuts, he explained to CNN: Their bodies would end up being overwhelmed with different pathways and chemistry than theyre used to, and theyd go crazy.

"We'll probably see a head on a robot before we see it on [another] body," he told Live Science.

Dr John Adler of Stanford University's school of medicine is slightly more optimistic... but not much more. "Conceptually, much of this could work, but the most favourable outcome will be little more than a Christopher Reeve level of function," he told Newsweek.

Canavero is aware of this criticism, claiming that silently hes received a lot of support from the medical community. Of Dr Batjers comments that the surgery would be a fate worse than death, Canavero is scathing. Hes a vascular surgeon. A vascular surgeon of the brain, yes, but he knows nothing, he argued. How can you say such a thing? Its incredible.

"The world is moving, the critics are dwindling. Of course, there will always be critics. Science teaches us that when you propose something groundbreaking, you must be confronted by criticism. If no critics really step forward, you are saying nothing special," he told Medical News Today.

Dr Canavero also believes that the operation could essentially be used to revive the dead, if brains were suitably frozen and stored. In an interview with German magazine Ooom, Canavero said: "We will try to bring the first of the company's patients back to life, not in 100 years. As soon as the first human head transplant has taken place, i.e. no later than 2018, we will be able to attempt to reawaken the first frozen head.We are currently planning the world's first brain transplant, and I consider it realistic that we will be ready in three years at the latest."

No-one has ever attempted a human head transplant before, and attempts on animals have to put it charitably had limited success.

Image: from Motherboard, uploaded under fair use from a 1959 issue of Life

The photo above really does show a dog with two heads and its not a fake. This was the work of Soviet scientist Vladimir Demikhov, and for four days the hybrid of two dogs lived as normally as such a scientific horror could be expected to. Then they died.

Demikhov tried the experiment more than 24 times, but was unable to find a way of avoiding the dogs dying shortly after surgery. Although the results are horrifying to see, Demikhovs research did pave the way for human organ transplants.

"For four days this hybrid of two dogs lived as normally as such a scientific horror could be expected to. Then they died."

But back to the topic of head transplants. The first time a straight swap was successful, was by Dr Robert White, in an experiment on a rhesus monkey in 1970. I feel the need to qualify the word successful with quotation marks, because although the monkey did live, he didnt live very long. Eight days, to be exact, and as the spinal cord wasnt attached to its new body, the monkey was paralysed for its remaining days. However, it could indeed see, hear, smell and taste before the body rejected the foreign head.

According to Canavero in his paper on human head transplants, the monkey lived eight days and was, by all measures, normal, having suffered no complications. However, Dr Jerry Silver who worked in the same lab as Dr White has more haunting memories. He toldCBS: I remember that the head would wake up, the facial expressions looked like terrible pain and confusion and anxiety in the animal. The head will stay alive, but not very long. It was just awful. I dont think it should ever be done again.

More recently, Chinese doctor Xiaoping Ren claims to have conducted head transplants on more than 1,000 mice. The Wall Street Journal reports to have witnessed a mouse with a new head moving, breathing, looking around and drinking. But, crucially, none of these mice have lived longer than a few minutes.

Still, Dr Rens studies continue, and the latest reports are said to be promising, offering a possible answer to the risk of severe blood loss (or brain ischemia) during transplantation. The experimental method that we have described can allow for long-term survival, and thus assessment of transplant rejection and central nervous system recovery, bringing us one step closer to AHBR in man, the researchers wrote.

Ren himself has not ruled out taking part in the first human head transplant operation, according to the Daily Mail. "A human head transplant will be a new frontier in science. Some people say it is the last frontier in medicine. It is a very sensitive and very controversial subject but if we can translate it to clinical practice, we can save a lot of lives," he said.

"Many people say a head transplant is not ethical. But what is the essence of a person? A person is the brain not the body. The body is just an organ," he added.

In January 2016, Canavero told New Scientist that a head transplant had been successfully completed on a monkey in China, although details were sparse. "The monkey fully survived the procedure without any neurological injury of whatever kind," he said, although the article notes that the monkey only kept alive for 20 hours after the surgery for "ethical reasons," limiting its use as a comparison somewhat.

In September 2016, Canavero revealeda further trial of the head transplant on dogs.New Scientisthas seen video footage of a dog appearing to walk three weeks after its spinal cord was severed, with Canavero claiming that the outcome is the result of the same techniques he plans to use on Spiridonov next year.

However, speaking to a number of scientists for their view on the new evidence, New Scientistcould find few sceptics converted. "These papers do not support moving forward in humans," said Jerry Silver a neuroscientist at Cape Western Reserve University in Ohio.

"The dog is a case report, and you cant learn very much from a single animal without controls. They claim they cut the cervical cord 90 per cent but theres no evidence of that in the paper, just some crude pictures," added Silver.

You could say so, though Canavero doesn't see it quite like that. In fact, controversially he sees it more as a failure of other types of medicine, telling Medical News Today, "It will be about curing incurable neurological disorders for which other treatments have failed big time, so gene therapy,stem cells- they all just came to nothing. We have failed despite billions of dollars being poured into this sort of research."

"So actually, head transplant or body transplant, whatever your angle is, is actually a failure of medicine. It is not a brilliant success, a brilliant advancement to medical science. When you just haven't tackled biology, you don't know how to treat genes, you don't really understand, and you really need to resort to a body transplant, it means that you've failed. So this must not be construed as a success of medical research," he added.

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Human head transplant: Dr Canavero considers Britain as the venue for 2017's most talked about operation - Alphr

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The DMC reviewed all of the accumulated safety data to date. The review included the safety data from six complete cervical injury (AIS-A) patients dosed with 10 million AST-OPC1 cells in Cohort 2, each of whom have completed at least six months of follow-up, as well as initial safety data from the currently enrolling Cohorts 3 and 4. Cohort 3 is enrolling AIS-A patients dosed with the highest dose of 20 million cells; Cohort 4 is testing 10 million cells in patients with less severe AIS-B incomplete cervical spinal cord injuries. In addition, the DMC reviewed the ongoing long-term safety data from the study's initial cohort of three patients dosed with 2 million cells, all of whom completed 12 months of follow-up in 2016.

As specified in the SCiStar study protocol, the DMC meets on a regular basis to review data from the ongoing trial. The DMC is comprised of an independent group of medical and scientific experts and is responsible for reviewing and evaluating patient safety and efficacy data for safeguarding the interest of study participants.

Asterias previously reported on positive early efficacy data from Cohort 2 (AIS-A; 10 million cells) of the SCiStar study. Patients from this cohort showed improvement in upper extremity motor function at 3-months following administration of AST-OPC1 and maintained or further increased this improvement at 6-months and 9-months. The results suggest a meaningful and favorable difference to date in recovery of arm, hand and finger function in patients treated with the 10 million cell dose of AST-OPC1 as compared to the level of expected rates of spontaneous recovery shown from historical control data of a closely matched patient population. Asterias expects to report additional efficacy and safety data for Cohort 2, as well as for the currently-enrolling Cohorts 3 and 4, later this year.

About the SCiStar Trial

The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 patients with sub-acute, C-5 to C-7, motor complete (AIS-A or AIS-B) cervical SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A patients have lost all motor and sensory function below their injury site, while AIS-B patients have lost all motor function but may retain some minimal sensory function below their injury site. AST-OPC1 is being administered 14 to 30 days post-injury. Patients will be followed by neurological exams and imaging procedures to assess the safety and activity of the product.

The study is being conducted at six centers in the U.S. and the company plans to increase this to up to 12 sites to accommodate the expanded patient enrollment. Clinical sites involved in the study include the Medical College of Wisconsin in Milwaukee, Shepherd Medical Center in Atlanta, University of Southern California (USC) jointly with Rancho Los Amigos National Rehabilitation Center in Los Angeles, Indiana University, Rush University Medical Center in Chicago and Santa Clara Valley Medical Center in San Jose jointly with Stanford University.

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

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

About AST-OPC1

AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells, has been shown in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hindlimb and forelimb locomotor function, dramatic reductions in injury-related cavitation and significant preservation of myelinated axons traversing the injury site.

In a previous Phase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million AST-OPC1 cells at the spinal cord injury site 7-14 days post-injury. They also received low levels of immunosuppression for the next 60 days. Delivery of AST-OPC1 was successful in all five subjects with no serious adverse events associated with AST-OPC1. No evidence of rejection of AST-OPC1 was observed in detailed immune response monitoring of all patients. In four of the five patients, serial MRI scans indicated that reduced spinal cord cavitation may have occurred. Based on the results of this study, Asterias received clearance from FDA to progress testing of AST-OPC1 to patients with complete cervical spine injuries, which represents the first targeted population for registration trials.

About Asterias Biotherapeutics

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

FORWARD-LOOKING STATEMENTS

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

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/asterias-biotherapeutics-announces-data-monitoring-committee-unanimously-recommends-continuation-of-scistar-phase-12a-clinical-trial-of-ast-opc1-for-cervical-spinal-cord-injury-300444644.html

SOURCE Asterias Biotherapeutics, Inc.

http://www.asteriasbiotherapeutics.com

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Asterias Biotherapeutics Announces Data Monitoring Committee Unanimously Recommends Continuation of SCiStar ... - PR Newswire (press release)

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The spinal cord is a rope of nerves relaying messages from the brain to every organ, muscle, and nerve ending in the body. The cells that make up the spinal cord arent a homogeneousmass, but rather a combination of dozens of specialized neurons, each with its own important role to play in guiding signals and impulses to the right destination.

This week, a team of California researchers announced the successful production of a lab-grown neuron that could help heal spinal cord injuries by reestablishing the connection between brain and muscle. In apaperpublished inProceedings of the National Academy of Sciences, researchers from the Gladstone Institutes and University of California campuses in San Francisco and Berkeley described how they grew human spinal cord neurons from stem cells and successfully introduced the lab-grown cells into the spines of healthy mice.

Todd McDevitt is a senior investigator at Gladstone and lead author of the study. He said that his team chose the targeted neuron, called a V2a interneuron, because it serves as a long relay cable between the neurons in the brain and the motor neurons that connect directly to muscle. V2a interneurons are, in fact, some of the longest cells in the body, able to extend their axon the nerve fibers that transmit electrical impulses across several vertebrae.

Its one cell stretching out up to 1,000 times longer than a normal human cell, said McDevitt. These outstretched neurons, as long as several centimeters, seem to play a critical role in relaying messages along the spinal cord. So if they are damaged in a traumatic injury, the brain-muscle connection may be severed, potentially leading to paralysis.

But if those critical V2a interneurons could be regenerated in an injured spine, the researchers wondered, perhaps the spinal cord could re-establish the connection and heal itself.

For the past three years, McDevitt and his team have been working to culture viable human V2a interneurons from pluripotent stem cells. The process, known as differentiation, attempts to replicate in the lab the natural development of neurons from undifferentiated stem cells in a human embryo.

Decades of research in developmental biology have provided clues to how genes in a developing embryo direct different proteins and other chemical factors to create all manner of specialized cells. The trouble is that most of the recipes for these chemical cocktails were derived from studying animal embryos.

Obviously, for good reasons, we dont do experiments on human embryos, McDevitt said. You have to take a leap of faith from the developmental biology knowledge we have from worms and flies and think about how we can apply that really important biological information to the human context.

RELATED:Brain Implant Helps 'Locked-In' ALS Woman Communicate

After experimenting with round after round of chemical combinations, the researchers landed on a process that can now produce a sizable batch of human V2a interneurons in a little over two weeks. The first step was to inject the cells into the spinal cords of healthy mice and see if the cells survived. They did even better.

Within two weeks, we saw a number of these cells extend their axons over long distances five millimeters reliably, but some even longer than that, McDevitt said, adding that the wiry cells are also making important connections. Even though theyre mice, we see these human cells that appear to be connecting to other neurons.

Does this mean were close to a human therapy using injections of healthy neurons to repair damaged spines? Not quite. Trials will first need to be run with injured mice before any human subjects can be tested. Plus, its entirely possible that V2a interneurons only fix very specific types of spinal injuries, or none at all. It might require the production of other spinal cord neurons, or a combination of several, to find the most effective treatment.

At the most basic level, this work shows that we can successfully introduce a new type of spinal neuron made from human pluripotent stem cells, McDevitt said. I see it as a step in whats probably going to be a much bigger effort by the field.

WATCH: Are We Close to Repairing Spinal Cord Injuries?

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Lab-Grown Neurons Could Help Heal Spinal Injuries and Restore Movement - Seeker

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Xianmin Zeng/Buck Inst.

Nerve cells derived from human stem cells, in work supported by the California Institute for Regenerative Medicine.

When California voters approved US$3billion in funding for stem-cell research in 2004, biologists flocked to the state, and citizens dreamed of cures for Parkinsons disease and spinal-cord injuries. Now, the pot of money one of the biggest state investments in science is running dry before treatments have emerged, raising questions about whether Californians will pour billions more into stem-cell research.

If they dont, that could leave hundreds of scientists without support, and strand potentially promising therapies before they reach the market. Its an issue of great concern, says Jonathan Thomas, chair of the board for the California Institute for Regenerative Medicine (CIRM) in Oakland.

CIRM is now doling out its final $650million, and its leaders are seeking money from the private sector to carry projects beyond 2020, when the money will run out. Advocates are also surveying voters to determine whether a new request for funding stands a chance in state elections next year. But critics argue against this way of funding research.

California voters saw major opportunities for stem cells in 2004 when they passed Proposition 71, which included an agreement to create the corporation that became CIRM. The move was a reaction to then-US president George W. Bushs decision in 2001 to restrict federal funds for work on human embryonic stem cells.

Since CIRM rolled out its first grants in 2006, it has funded more than 750 projects and reported alluring results from clinical trials. In March, a trial partially funded by CIRM showed that nine out of ten children born with severe combined immunodeficiency or bubble-boy disease a potentially lethal condition in which a persons immune system does not function properly, were doing well up to eight years after treatment (K.L.Shaw etal. J. Clin. Invest. http://doi.org/b6bp; 2017). They no longer need injections to be able to go to school, play outside or survive colds and other inevitable infections.

A dozen facilities constructed by CIRM have helped to push California to the forefront of research on ageing and regenerative medicine. Many grant recipients were early-career academics who had not been able to enter the stem-cell field previously because of the federal restrictions which were loosened in 2009 and the high cost of getting started in this kind of work. That barrier makes it difficult for researchers to gather the preliminary data typically required to win grants from the US National Institutes of Health (NIH).

To milk its remaining $650 million, CIRM partnered last year with the contract-research organization QuintilesIMS in Durham, North Carolina, to carry out clinical trials. CIRM leaders hope that this move will help to guide 40 novel therapies into trials by 2020.

Bob Klein, the property developer who put Proposition 71 on the ballot and established CIRM, isnt waiting for the money to run out. He leads an advocacy group, Americans for Cures, which will soon poll voters to see whether they would approve another $5 billion in funding. If it looks like at least 70% of Californians support that plan, hell start a campaign to put another initiative on the ballot in 2018.

Klein hopes that Californians will rise in support of science at a time when the Trump administration has proposed drastic cuts to the NIH budget. If public enthusiasm is not so strong, Klein says, hell aim for the 2020 elections, when voter turnout should be higher because it will coincide with the next presidential race.

Currently, CIRMs leaders are seeking other sources of support. The majority of our projects will not be ripe for interest from big pharma and the venture-capitalist community by the time we run out of funds, Thomas says. He has been courting large philanthropic foundations and wealthy individuals to raise money to continue the work.

John Simpson, who directs stem-cell oversight work at the advocacy group Consumer Watchdog in Washington DC, plans to oppose any effort to extend CIRM. I acknowledge their scientific advances, but we should not let a flawed process go further, he says. Simpson dislikes the model of using a vote to secure research funding through public bonds, because then the state lacks budgetary control.

Oversight of CIRM has been a problem in the past. In 2012, the US Institute of Medicine found that some scientists vetting grant proposals for CIRM had conflicts of interest. In response, CIRM altered its procedures but the public still felt betrayed. Jim Lott, a member of the state board that oversees CIRMs finances, says that he is not satisfied with the changes. He also argues that CIRM may not have been strategic enough in directing research. Some people say if they had a better focus, they might have achieved cures.

But researchers argue that expectations for cures after only a decade are unrealistic, given the typical pace of drug development. It would be a catastrophe for California if people say CIRM did not do what it was expected to do, says Eric Verdin, president of the Buck Institute for Research on Aging in Novato, California. Theyve built the foundation for the field and attracted people from around the world you cant just now pull the plug.

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Discovery offers new hope to repair spinal cord injuries: Scientists ... Science Daily Scientists have created a special type of neuron from human stem cells that could potentially repair spinal cord injuries. These cells, called V2a interneurons, ... and more »

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WSU student fractured spine at Oxford party

Ryan Custer, a Wright State University student who was severely injured at an Oxford party, is being considered for a stem cell study at Rush University Hospital in Chicago. The 19-year-old, a first-year forward for the Raiders varsity basketball team, will be evaluated for five days before doctors determine if he qualifies for the study.

Custer suffered a severe spinal injury after jumping into a makeshift pool at a party on S. Main Street on Saturday, April 8. Custer collided with another persons knee when he slid into the pool, causing the injury. Custer was immediately transported to the University of Cincinnati Medical Center where he underwent surgery on his spine that night.

Feeling in Custers legs has not returned, and he has only recently regained some movement in his fingers.

Custer was transported from the UC Medical Center to Rush Hospital on Sunday, April 22. According to a post from the Ryan Custer Recovery Care Page, a Facebook page updated almost daily by Custers family, he spent the first day in Chicago getting acclimated in his new room in Rushs ICU and meeting the doctor who will lead the study, Dr. Richard Fessler.

Dr. Fessler, a renowned spinal surgeon, has focused his research on developing and refining new ways to perform minimally invasive spinal surgeries. In 2010, Fessler performed surgery on former Indianapolis Colts quarterback Peyton Manning, which Custer was happy to learn, the post said.

The five-day period of testing began Monday, and, if selected for the study, treatment for Custer will begin on Friday. The study, called the SCiStar study, will evaluate how the injection of AST-OPC1, particular neural cells produced from human embryonic stem cells, at a single time 14 to 30 days after an injury can benefit the patients recovery.

According to the SCiStar webpage, the studys researchers are seeking adults between the ages of 18 and 69 who recently experienced a spinal cord injury in the neck which resulted in a loss of feeling below the site of the injury in addition to some paralysis in the arms and legs.

HBO has contacted Dr. Fessler about following a patient through this research process.

Ryan thinks it would be cool to do it, so we said yes,an April 22 Facebook post reads. Another step in the plan God has mapped out for Ryan.

A fundraising page created for Custer, The Ryan Custer 33 Recovery Fund, is close to raising its entire $100,000 goal. At the time of publication, the fund was just about $4,000 shy of the 100k mark.

Over 6,500 people have liked the page and are following along with Custers recovery through the familys Facebook updates.

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By Marilynn Marchione The Associated Press

Tummy tucks really hurt. Doctors carve from hip to hip, slicing off skin, tightening muscles, tugging at innards.

Patients often need strong painkillers for days or even weeks, after the procedure but Mary Hernandez went home on just over-the-counter ibuprofen.

The reason could be the yellowish goo smeared on her 18-inch wound as she lay on the operating table. The Houston woman was helping test a novel medicine aimed at avoiding opioids, potent pain relievers fueling an epidemic of overuse and addiction.

Vicodin, OxyContin and similar drugs are widely used for bad backs, severe arthritis, damaged nerves and other ailments. They work powerfully in brain areas that control pleasure and pain, but the body adapts to them quickly, so people need higher and higher doses to get relief.

This growing dependence on opioids has mushroomed into a national health crisis, ripping apart communities and straining police and health departments.

Every day, an overdose of prescription opioids or heroin kills 91 people, and legions more are brought back from the brink of death. With some 2 million Americans hooked on these pills, evidence is growing that theyre not as good a choice for treating chronic pain as once thought.

Drug companies are working on alternatives, but have had little success.

Twenty or so years ago, they invested heavily and failed miserably, said Dr. Nora Volkow, director of the National Institute on Drug Abuse.

Pain is a pain to research. Some people bear more than others, and success cant be measured as objectively as it can be with medicines that shrink a tumor or clear an infection. Some new pain drugs that worked well were doomed by side effects Vioxx, for example, helped arthritis but hurt hearts.

Some fresh approaches are giving hope:

Bespoke drugs, as Volkow calls them. These target specific pathways and types of pain rather than acting broadly in the brain. One is Enbrel, which treats a key feature of rheumatoid arthritis and, in the process, eases pain.

Drugs to prevent the need for opioids. One that Hernandez was helping test numbs a wound for a few days and curbs inflammation. If people dont have big pain after surgery, their nerves dont go on high alert and theres less chance of developing chronic pain that might require opioids.

Funky new sources for medicines. In testing: Drugs from silk, hot chili peppers and the venom of snakes, snails and other critters.

Novel uses for existing drugs. Some seizure and depression medicines, for example, can help some types of pain.

The biggest need, however, is for completely new medicines that can be used by lots of people for lots of problems. These also pose the most risk for companies and patients alike.

Bumpy road

In the early 2000s, a small biotech company had a big idea: blocking nerve growth factor, a protein made in response to pain.

The companys drug, now called tanezumab, works on outlying nerves, helping to keep pain signals from muscles, skin and organs from reaching the spinal cord and brain good for treating arthritis and bad backs.

Pfizer Inc. bought the firm in 2006 and expanded testing. But in 2010, some people on tanezumab and similar drugs being tested by rivals needed joint replacements.

Besides dulling pain, nerve growth factor might affect joint repair and regeneration, so a possible safety issue needed full investigation in a medicine that would be the first of its type ever sold, said one independent expert, Dr. Jianguo Cheng, a Cleveland Clinic pain specialist and science chief for the American Academy of Pain Medicine.

Regulators put some of the studies on hold. Suddenly, some people who had been doing well on tanezumab lost access to it. Phyllis Leis in Waterfall, a small town in south-central Pennsylvania, was one.

I was so angry, she said. That was like a miracle drug. It really was. Unless you have arthritis in your knees and have trouble walking, youll never understand how much relief and what a godsend it was.

Her doctor, Alan Kivitz of the Altoona Center for Clinical Research, has helped run hundreds of pain studies and consults for Pfizer and many other companies.

You rarely get people to feel that good as many of them did on the nerve growth factor drugs, he said.

A drug with that much early promise is unusual, said Ken Verburg, who has led Pfizers pain research for several decades. When you do see one, you fight hard to try to bring one to the market, he said.

An independent review ultimately tied just a few serious joint problems to tanezumab and the suspension on testing was lifted in August 2012. But a new issue nervous system effects in some animal studies prompted a second hold later that year, and that wasnt lifted until 2015.

Now, Eli Lilly & Co. has joined Pfizer in testing tanezumab in late-stage studies with 7,000 patients. Results are expected late next year about 17 years after the drugs conception.

Avoiding pain

What if a drug could keep people from needing long-term pain relief in the first place? Heron Therapeutics Inc. is testing a novel, long-acting version of two drugs the anesthetic bupivacaine and the anti-inflammatory meloxicam for notoriously painful operations such as tummy tucks, bunion removal and hernia repair.

Company studies suggest it can numb wounds for about three days and cut patients need for opioids by 30 to 50 percent.

Theres a good chance of preventing brain responses that lead to chronic pain if patients can get through that initially very rough period, said Dr. Harold Minkowitz, a Houston anesthesiologist who consults for Heron and treated Hernandez in the tummy tuck study.

Hernandez was part of an experiment testing the drug vs. a placebo and doesnt know whether she got the drug or a dummy medicine. But she hurt less than she expected to and never filled a prescription for pain pills.

The goal would be to have half or more of patients not requiring an opiate after they go home, said Herons chief executive, Barry Quart. You have far fewer opiates going out into society, far fewer opiates sitting in medicine cabinets that make their way to a high school.

Studies so far are mid-stage too small to prove safety and effectiveness but Heron plans more aimed at winning approval.

On the horizon

Many companies have their eyes on sodium channel blockers, which affect how nerves talk to one another and thus might help various types of pain. Others are testing cell therapies for nerve pain. Stem cells can modulate immune responses and inflammation, and might overcome a raft of problems, said Cheng of the pain medicine academy.

Some companies, including Samumed, Centrexion Therapeutics and Flexion Therapeutics, are testing long-acting medicines to inject in knees to relieve arthritis pain. Samumeds aims to regenerate cartilage.

And then theres marijuana. A cannabis extract is sold as a mouth spray in Britain for nerve pain and other problems from multiple sclerosis. But cannabinoid research in the United States has been hampered by marijuanas legal status. A special license is needed and most researchers dont even try to obtain one, said Susan Ingram, a neurosurgery scientist at Oregon Health & Science University.

She is studying cannabinoid receptors in the brain, looking at how pain affects one type but not another. Such work might someday lead to drugs that relieve pain but dont produce a high or addiction.

Selective activity has precedent: The drug buprenorphine partially binds to opioid receptors in the brain and has become an extraordinarily successful medication for treating addiction, said Volkow, of the national drug institute.

It has shown pharmaceutical companies that if you come up with a good intervention, there is an opportunity to recover their costs, she said.

Tummy tucks really hurt. Doctors carve from hip to hip, slicing off skin, tightening muscles, tugging at innards. Patients often need strong painkillers for days or even weeks, after the procedure but Mary Hernandez went home on just over-the-counter ibuprofen. The reason could be the yellowish goo smeared on her 18-inch wound as she lay on the operating table. The Houston woman was helping test a novel medicine aimed at avoiding opioids, potent pain relievers fueling an epidemic of overuse and addiction. Vicodin, OxyContin and similar drugs are widely used for bad backs, severe arthritis, damaged nerves and other ailments. They work powerfully in brain areas that control pleasure and pain, but the body adapts to them quickly, so people need higher and higher doses to get relief. This growing dependence on opioids has mushroomed into a national health crisis, ripping apart communities and straining police and health departments. Every day, an overdose of prescription opioids or heroin kills 91 people, and legions more are brought back from the brink of death. With some 2 million Americans hooked on these pills, evidence is growing that theyre not as good a choice for treating chronic pain as once thought. Drug companies are working on alternatives, but have had little success. Twenty or so years ago, they invested heavily and failed miserably, said Dr. Nora Volkow, director of the National Institute on Drug Abuse. Pain is a pain to research. Some people bear more than others, and success cant be measured as objectively as it can be with medicines that shrink a tumor or clear an infection. Some new pain drugs that worked well were doomed by side effects Vioxx, for example, helped arthritis but hurt hearts. Some fresh approaches are giving hope: n Bespoke drugs, as Volkow calls them. These target specific pathways and types of pain rather than acting broadly in the brain. One is Enbrel, which treats a key feature of rheumatoid arthritis and, in the process, eases pain. n Drugs to prevent the need for opioids. One that Hernandez was helping test numbs a wound for a few days and curbs inflammation. If people dont have big pain after surgery, their nerves dont go on high alert and theres less chance of developing chronic pain that might require opioids. n Funky new sources for medicines. In testing: Drugs from silk, hot chili peppers and the venom of snakes, snails and other critters. n Novel uses for existing drugs. Some seizure and depression medicines, for example, can help some types of pain. The biggest need, however, is for completely new medicines that can be used by lots of people for lots of problems. These also pose the most risk for companies and patients alike.Subhead: Bumpy road In the early 2000s, a small biotech company had a big idea: blocking nerve growth factor, a protein made in response to pain. The companys drug, now called tanezumab, works on outlying nerves, helping to keep pain signals from muscles, skin and organs from reaching the spinal cord and brain good for treating arthritis and bad backs. Pfizer Inc. bought the firm in 2006 and expanded testing. But in 2010, some people on tanezumab and similar drugs being tested by rivals needed joint replacements. Besides dulling pain, nerve growth factor might affect joint repair and regeneration, so a possible safety issue needed full investigation in a medicine that would be the first of its type ever sold, said one independent expert, Dr. Jianguo Cheng, a Cleveland Clinic pain specialist and science chief for the American Academy of Pain Medicine. Regulators put some of the studies on hold. Suddenly, some people who had been doing well on tanezumab lost access to it. Phyllis Leis in Waterfall, a small town in south-central Pennsylvania, was one. I was so angry, she said. That was like a miracle drug. It really was. Unless you have arthritis in your knees and have trouble walking, youll never understand how much relief and what a godsend it was. Her doctor, Alan Kivitz of the Altoona Center for Clinical Research, has helped run hundreds of pain studies and consults for Pfizer and many other companies. You rarely get people to feel that good as many of them did on the nerve growth factor drugs, he said. A drug with that much early promise is unusual, said Ken Verburg, who has led Pfizers pain research for several decades. When you do see one, you fight hard to try to bring one to the market, he said. An independent review ultimately tied just a few serious joint problems to tanezumab and the suspension on testing was lifted in August 2012. But a new issue nervous system effects in some animal studies prompted a second hold later that year, and that wasnt lifted until 2015. Now, Eli Lilly & Co. has joined Pfizer in testing tanezumab in late-stage studies with 7,000 patients. Results are expected late next year about 17 years after the drugs conception.Subhead: Avoiding pain What if a drug could keep people from needing long-term pain relief in the first place? Heron Therapeutics Inc. is testing a novel, long-acting version of two drugs the anesthetic bupivacaine and the anti-inflammatory meloxicam for notoriously painful operations such as tummy tucks, bunion removal and hernia repair. Company studies suggest it can numb wounds for about three days and cut patients need for opioids by 30 to 50 percent. Theres a good chance of preventing brain responses that lead to chronic pain if patients can get through that initially very rough period, said Dr. Harold Minkowitz, a Houston anesthesiologist who consults for Heron and treated Hernandez in the tummy tuck study. Hernandez was part of an experiment testing the drug vs. a placebo and doesnt know whether she got the drug or a dummy medicine. But she hurt less than she expected to and never filled a prescription for pain pills. The goal would be to have half or more of patients not requiring an opiate after they go home, said Herons chief executive, Barry Quart. You have far fewer opiates going out into society, far fewer opiates sitting in medicine cabinets that make their way to a high school. Studies so far are mid-stage too small to prove safety and effectiveness but Heron plans more aimed at winning approval.Subhead: On the horizon Many companies have their eyes on sodium channel blockers, which affect how nerves talk to one another and thus might help various types of pain. Others are testing cell therapies for nerve pain. Stem cells can modulate immune responses and inflammation, and might overcome a raft of problems, said Cheng of the pain medicine academy. Some companies, including Samumed, Centrexion Therapeutics and Flexion Therapeutics, are testing long-acting medicines to inject in knees to relieve arthritis pain. Samumeds aims to regenerate cartilage. And then theres marijuana. A cannabis extract is sold as a mouth spray in Britain for nerve pain and other problems from multiple sclerosis. But cannabinoid research in the United States has been hampered by marijuanas legal status. A special license is needed and most researchers dont even try to obtain one, said Susan Ingram, a neurosurgery scientist at Oregon Health & Science University. She is studying cannabinoid receptors in the brain, looking at how pain affects one type but not another. Such work might someday lead to drugs that relieve pain but dont produce a high or addiction. Selective activity has precedent: The drug buprenorphine partially binds to opioid receptors in the brain and has become an extraordinarily successful medication for treating addiction, said Volkow, of the national drug institute. It has shown pharmaceutical companies that if you come up with a good intervention, there is an opportunity to recover their costs, she said.

See the original post here:
Researchers look for new ways to reduce suffering, end addiction ... - The Columbus Dispatch

Spinal Cord Stem Cells Comments Off on Researchers look for new ways to reduce suffering, end addiction … – The Columbus Dispatch | April 23rd, 2017

By Marilynn MarchioneAP Chief Medical Writer

Tummy tucks really hurt. Doctors carve from hip to hip, slicing off skin, tightening muscles, tugging at innards. Patients often need strong painkillers for days or even weeks, but Mary Hernandez went home on just over-the-counter ibuprofen.

The reason may be the yellowish goo smeared on her 18-inch wound as she lay on the operating table. The Houston woman was helping test a novel medicine aimed at avoiding opioids, potent pain relievers fueling an epidemic of overuse and addiction.

Vicodin, OxyContin and similar drugs are widely used for bad backs, severe arthritis, damaged nerves and other woes. They work powerfully in brain areas that control pleasure and pain, but the body adapts to them quickly, so people need higher and higher doses to get relief.

This growing dependence on opioids has mushroomed into a national health crisis, ripping apart communities and straining police and health departments. Every day, an overdose of prescription opioids or heroin kills 91 people, and legions more are brought back from the brink of death. With some 2 million Americans hooked on these pills, evidence is growing that they're not as good a choice for treating chronic pain as once thought.

Drug companies are working on alternatives, but have had little success.

Twenty or so years ago, they invested heavily and "failed miserably," said Dr. Nora Volkow, director of the National Institute on Drug Abuse.

Pain is a pain to research. Some people bear more than others, and success can't be measured as objectively as it can be with medicines that shrink a tumor or clear an infection. Some new pain drugs that worked well were doomed by side effects Vioxx, for instance, helped arthritis but hurt hearts.

Some fresh approaches are giving hope:

"Bespoke" drugs, as Volkow calls them. These target specific pathways and types of pain rather than acting broadly in the brain. One is Enbrel, which treats a key feature of rheumatoid arthritis and, in the process, eases pain.

Drugs to prevent the need for opioids. One that Hernandez was helping test numbs a wound for a few days and curbs inflammation. If people don't have big pain after surgery, their nerves don't go on high alert and there's less chance of developing chronic pain that might require opioids.

Funky new sources for medicines. In testing: Drugs from silk, hot chili peppers and the venom of snakes, snails and other critters.

Novel uses for existing drugs. Some seizure and depression medicines, for example, can help some types of pain.

The biggest need, however, is for completely new medicines that can be used by lots of people for lots of problems. These also pose the most risk for companies and patients alike.

One drug's bumpy road

In the early 2000s, a small biotech company had a big idea: blocking nerve growth factor, a protein made in response to pain. The company's drug, now called tanezumab (tah-NAZE-uh-mab), works on outlying nerves, helping to keep pain signals from muscles, skin and organs from reaching the spinal cord and brain good for treating arthritis and bad backs.

Pfizer Inc. bought the firm in 2006 and expanded testing. But in 2010, some people on tanezumab and similar drugs being tested by rivals needed joint replacements. Besides dulling pain, nerve growth factor may affect joint repair and regeneration, so a possible safety issue needed full investigation in a medicine that would be the first of its type ever sold, said one independent expert, Dr. Jianguo Cheng, a Cleveland Clinic pain specialist and science chief for the American Academy of Pain Medicine.

Regulators put some of the studies on hold. Suddenly, some people who had been doing well on tanezumab lost access to it. Phyllis Leis in Waterfall, a small town in south-central Pennsylvania, was one.

"I was so angry," she said. "That was like a miracle drug. It really was. Unless you have arthritis in your knees and have trouble walking, you'll never understand how much relief and what a godsend it was."

Her doctor, Alan Kivitz of Altoona Center for Clinical Research, has helped run hundreds of pain studies and consults for Pfizer and many other companies. "You rarely get people to feel that good" as many of them did on the nerve growth factor drugs, he said.

A drug with that much early promise is unusual, said Ken Verburg, who has led Pfizer's pain research for several decades.

"When you do see one, you fight hard to try to bring one to the market," he said.

An independent review ultimately tied just a few serious joint problems to tanezumab and the suspension on testing was lifted in August 2012. But a new issue nervous system effects in some animal studies prompted a second hold later that year, and that wasn't lifted until 2015.

Now Eli Lilly & Co. has joined Pfizer in testing tanezumab in late-stage studies with 7,000 patients. Results are expected late next year about 17 years after the drug's conception.

Avoiding pain to avoid drugs

What if a drug could keep people from needing long-term pain relief in the first place? Heron Therapeutics Inc. is testing a novel, long-acting version of two drugs the anesthetic bupivacaine and the anti-inflammatory meloxicam for notoriously painful operations like tummy tucks, bunion removal and hernia repair.

Company studies suggest it can numb wounds for about three days and cut patients' need for opioids by 30 percent to 50 percent.

There's a good chance of preventing brain responses that lead to chronic pain if patients can get through that "initially very rough period," said Dr. Harold Minkowitz, a Houston anesthesiologist who consults for Heron and treated Hernandez in the tummy tuck study.

Hernandez was part of an experiment testing the drug versus a placebo and doesn't know whether she got the drug or a dummy medicine. But she hurt less than she expected to and never filled a prescription for pain pills.

"The goal would be to have half or more of patients not requiring an opiate after they go home," said Heron's chief executive, Barry Quart. "You have far fewer opiates going out into society, far fewer opiates sitting in medicine cabinets that make their way to a high school."

Studies so far are mid-stage too small to prove safety and effectiveness but Heron plans more aimed at winning approval.

On the horizon

Many companies have their eyes on sodium channel blockers, which affect how nerves talk to each other and thus might help various types of pain. Others are testing cell therapies for nerve pain. Stem cells can modulate immune responses and inflammation, and may "overcome a raft of problems," said Cheng of the pain medicine academy.

Some companies, including Samumed, Centrexion Therapeutics and Flexion Therapeutics, are testing long-acting medicines to inject in knees to relieve arthritis pain. Samumed's aims to regenerate cartilage.

And then there's marijuana. A cannabis extract is sold as a mouth spray in Britain for nerve pain and other problems from multiple sclerosis. But cannabinoid research in the United States has been hampered by marijuana's legal status. A special license is needed and most researchers don't even try to obtain one, said Susan Ingram, a neurosurgery scientist at Oregon Health & Science University.

She is studying cannabinoid receptors in the brain, looking at how pain affects one type but not another. Such work might someday lead to drugs that relieve pain but don't produce a high or addiction.

Selective activity has precedent: The drug buprenorphine partially binds to opioid receptors in the brain and has become "an extraordinarily successful medication" for treating addiction, said Volkow, of the national drug institute.

"It has shown pharmaceutical companies that if you come up with a good intervention, there is an opportunity to recover their costs," she said.

Marilynn Marchione can be followed at http://twitter.com/MMarchioneAP

Here is the original post:
The quest for less addictive drugs - Foster's Daily Democrat

Spinal Cord Stem Cells Comments Off on The quest for less addictive drugs – Foster’s Daily Democrat | April 23rd, 2017

Tummy tucks really hurt. Doctors carve from hip to hip, slicing off skin, tightening muscles, tugging at innards. Patients often need strong painkillers for days or even weeks, but Mary Hernandez went home on just over-the-counter ibuprofen.

The reason may be the yellowish goo smeared on her 18-inch wound as she lay on the operating table. The Houston woman was helping test a novel medicine aimed at avoiding opioids, potent pain relievers fueling an epidemic of overuse and addiction.

Vicodin, OxyContin and similar drugs are widely used for bad backs, severe arthritis, damaged nerves and other woes. They work powerfully in brain areas that control pleasure and pain, but the body adapts to them quickly, so people need higher and higher doses to get relief.

This growing dependence on opioids has mushroomed into a national health crisis, ripping apart communities and straining police and health departments. Every day, an overdose of prescription opioids or heroin kills 91 people, and legions more are brought back from the brink of death. With about

2 million Americans hooked on these pills, evidence is growing that theyre not as good a choice for treating chronic pain as once thought.

Drug companies are working on alternatives, but have had little success.

Twenty or so years ago, they invested heavily and failed miserably, said Dr. Nora Volkow, director of the National Institute on Drug Abuse.

Pain is a pain to research. Some people bear more than others, and success cant be measured as objectively as it can be with medicines that shrink a tumor or clear an infection. Some new pain drugs that worked well were doomed by side effects Vioxx, for instance, helped arthritis but hurt hearts.

Some fresh approaches are giving hope:

Bespoke drugs, as Volkow calls them. These target specific pathways and types of pain rather than acting broadly in the brain. One is Enbrel, which treats a key feature of rheumatoid arthritis and, in the process, eases pain.

Drugs to prevent the need for opioids. One that Hernandez was helping test numbs a wound for a few days and curbs inflammation. If people dont have big pain after surgery, their nerves dont go on high alert and theres less chance of developing chronic pain that might require opioids.

Funky new sources for medicines. In testing: Drugs from silk, hot chili peppers and the venom of snakes, snails and other critters.

Novel uses for existing drugs. Some seizure and depression medicines, for example, can help some types of pain.

The biggest need, however, is for completely new medicines that can be used by lots of people for lots of problems. These also pose the most risk for companies and patients alike.

ONE DRUGS BUMPY ROAD

In the early 2000s, a small biotech company had a big idea: blocking nerve growth factor, a protein made in response to pain.

The companys drug, now called tanezumab, works on outlying nerves, helping to keep pain signals from muscles, skin and organs from reaching the spinal cord and brain good for treating arthritis and bad backs.

Pfizer Inc. bought the firm in 2006 and expanded testing. But in 2010, some people on tanezumab and similar drugs being tested by rivals needed joint replacements. Besides dulling pain, nerve growth factor may affect joint repair and regeneration, so a possible safety issue needed full investigation in a medicine that would be the first of its type ever sold, said one independent expert, Dr. Jianguo Cheng, a Cleveland Clinic pain specialist and science chief for the American Academy of Pain Medicine.

Regulators put some of the studies on hold. Suddenly, some people who had been doing well on tanezumab lost access to it. Phyllis Leis in Waterfall, a small town in south-central Pennsylvania, was one.

I was so angry, she said. That was like a miracle drug. It really was. Unless you have arthritis in your knees and have trouble walking, youll never understand how much relief and what a godsend it was.

Her doctor, Alan Kivitz of Altoona Center for Clinical Research, has helped run hundreds of pain studies and consults for Pfizer and many other companies.

You rarely get people to feel that good as many of them did on the nerve growth factor drugs, he said.

A drug with that much early promise is unusual, said Ken Verburg, who has led Pfizers pain research for several decades.

When you do see one, you fight hard to try to bring one to the market, he said.

An independent review ultimately tied just a few serious joint problems to tanezumab and the suspension on testing was lifted in August 2012. But a new issue nervous system effects in some animal studies prompted a second hold later that year, and that wasnt lifted until 2015.

Now Eli Lilly & Co. has joined Pfizer in testing tanezumab in late-stage studies with 7,000 patients.

Results are expected late next year about 17 years after the drugs conception.

AVOIDING PAIN AND DRUGS

What if a drug could keep people from needing long-term pain relief in the first place? Heron Therapeutics Inc. is testing a novel, long-acting version of two drugs the anesthetic bupivacaine and the anti-inflammatory meloxicam for notoriously painful operations like tummy tucks, bunion removal and hernia repair.

Company studies suggest it can numb wounds for about three days and cut patients need for opioids by 30 to 50 percent.

Theres a good chance of preventing brain responses that lead to chronic pain if patients can get through that initially very rough period, said Dr. Harold Minkowitz, a Houston anesthesiologist who consults for Heron and treated Hernandez in the tummy tuck study.

Hernandez was part of an experiment testing the drug versus a placebo and doesnt know whether she got the drug or a dummy medicine. But she hurt less than she expected to and never filled a prescription for pain pills.

The goal would be to have half or more of patients not requiring an opiate after they go home, said Herons chief executive, Barry Quart. You have far fewer opiates going out into society, far fewer opiates sitting in medicine cabinets that make their way to a high school.

Studies so far are mid-stage too small to prove safety and effectiveness but Heron plans more aimed at winning approval.

ON THE HORIZON

Many companies have their eyes on sodium channel blockers, which affect how nerves talk to each other and thus might help various types of pain. Others are testing cell therapies for nerve pain. Stem cells can modulate immune responses and inflammation, and may overcome a raft of problems, said Cheng of the pain medicine academy.

Some companies, including Samumed, Centrexion Therapeutics and Flexion Therapeutics, are testing long-acting medicines to inject in knees to relieve arthritis pain. Samumeds aims to regenerate cartilage.

And then theres marijuana. A cannabis extract is sold as a mouth spray in Britain for nerve pain and other problems from multiple sclerosis. But cannabinoid research in the U.S. has been hampered by marijuanas legal status. A special license is needed and most researchers dont even try to obtain one, said Susan Ingram, a neurosurgery scientist at Oregon Health & Science University.

She is studying cannabinoid receptors in the brain, looking at how pain affects one type but not another. Such work might someday lead to drugs that relieve pain but dont produce a high or addiction.

Selective activity has precedent: The drug buprenorphine partially binds to opioid receptors in the brain and has become an extraordinarily successful medication for treating addiction, said Volkow, of the national drug institute.

It has shown pharmaceutical companies that if you come up with a good intervention, there is an opportunity to recover their costs, she said.

More:
Overcoming opioids: Quest for less addictive drugs - Mohave Valley News

Spinal Cord Stem Cells Comments Off on Overcoming opioids: Quest for less addictive drugs – Mohave Valley News | April 23rd, 2017

FINDINGS

New research by scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLAoverturns a long-standing paradigm about how axons thread-like projections that connect cells in the nervous system grow during embryonic development. The findings of the study, led by Samantha Butler, associate professor of neurobiology, could help scientists replicate or control the way axons grow, which may be applicable for diseases that affect the nervous system, such as diabetes, as well as injuries that sever nerves.

As an embryo grows, neurons the cells in the nervous system extend axons into the developing spinal cord. Axons are then guided to reach other areas of the body, such as the brain, to establish a functioning nervous system. It has been generally understood that various guidance cues, which are cellular molecules such as proteins, either attract or repel axon growth as the axons reach out from neurons to find their destination in the nervous system.

Previous research suggested that a particular guidance cue, called netrin1, functions over a long distance to attract and organize axon growth, similar to how a lighthouse sends out a signal to orient a ship from afar. However, previous research also shows that netrin1 is produced in many places in the embryonic spinal cord, raising questions about whether it really acts over a long distance. Most notably, netrin1 is produced by tissue-specific stem cells, called neural progenitors, which can create any cell type in the nervous system. Yet, it was not understood how the netrin1 produced by neural progenitors influences axon growth.

Butler and her research team removed netrin1 from neural progenitors in different areas in mouse embryonic spinal cords. This manipulation resulted in highly disorganized and abnormal axon growth, giving the researchers a very detailed view of how netrin1 produced by neural progenitors influences axons in the developing nervous system.

They found that neural progenitors organize axon growth by producing a pathway of netrin1 that directs axons only in their local environment and not over long distances. This pathway of netrin1 acts as a sticky surface that encourages axon growth in the directions that form a normal, functioning nervous system.

Butlers study is a significant reinterpretation of the role of netrin1 in nervous system formation. The results further scientists understanding of the contribution neural progenitors make to neural circuit formation. Determining how netrin1 specifically influences axon growth could help scientists use netrin1 to regenerate axons more effectively in patients whose nerves have been damaged.

For example, because nerves grow in channels, there is much interest in trying to restore nerve channels after an injury that results in severed nerves, which is seen often in patients who have experienced an accident or in veterans with injuries to their arms or legs. One promising approach is to implant artificial nerve channels into a person with a nerve injury to give regenerating axons a conduit to grow through. Butler believes that coating such nerve channels with netrin1 could further encourage axon regrowth. Her continued research will focus on uncovering more details about how netrin1 functions and how it could be used clinically.

Butler is the senior author of the study. The first author is Supraja Varadarajan, a graduate student in Butlers lab.

The study is published today in the journal Neuron.

The study was funded by grants from the National Institutes of Health (DK097075, HL098294, HL114457, DK082509 HL109233, DK109574, HL119837, NS072804, NS089817, NS063999, NS085097 and HL133900), the Canadian Institutes of Health Research (MOP-97758 and MOP-77556), Brain Canada, the Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation, the W. Garfield Weston Foundation, the March of Dimes Foundation (6-FY10-296 and 1-FY07-458) and the UCLA Broad Stem Cell Research Center.

See more here:
Study overturns seminal research about the developing nervous system - UCLA Newsroom

Spinal Cord Stem Cells Comments Off on Study overturns seminal research about the developing nervous system – UCLA Newsroom | April 21st, 2017