Vistagen Therapeutics Successfully Completes Final Phase 1 Safety Study of AV-101

SOUTH SAN FRANCISCO, CA--(Marketwire - Jan 23, 2013) - VistaGen Therapeutics, Inc. ( OTCQB : VSTA ), a biotechnology company applying stem cell technology for drug rescue, predictive toxicology and drug metabolism screening, today announced the successful completion of its final Phase 1 safety study of AV-101, a novel orally available prodrug candidate being developed for treatment of multiple conditions involving chronic neuropathic pain.The study results indicate that AV-101 is safe and well tolerated, with favorable bioavailability and pharmacokinetics.

"This important confirmation of AV-101's safety is the final step in our Phase 1 program for AV-101," said Shawn K. Singh, JD, VistaGen's Chief Executive Officer. "With $8.8 million of funding from the National Institutes of Health (NIH) and outstanding strategic development and regulatory support from Cato Research Ltd., we have successfully completed the required studies enabling Phase 2 clinical development of AV-101 for multiple large market neurological diseases and conditions.In addition, recent data from the NIH suggest that the same neural pathway modified by AV-101 may be useful for treating depression.Launching a broad strategic collaboration to advance development and commercialization of AV-101 is among our key goals in 2013."

About the Final AV-101 Phase 1 Safety Study

VistaGen's final AV-101 Phase 1 safety study was a randomized, double-blind, placebo-controlled, dose-escalation clinical trial conducted at the University of California, San Diego (UCSD).The study involved three cohorts of healthy volunteers, each receiving multiple daily treatments of one of three dose levels of orally administered AV-101 over a 14-day period. The primary objectives of the study were to evaluate the safety, tolerability and pharmacokinetics (PK) of three different daily doses of AV-101 compared to placebo controls.A total of 46 healthy volunteers completed the study.The oral administration of AV-101 was safe and well tolerated by all subjects at all three dose levels tested.In addition, the PK of AV-101 was fully characterized across the range of three dose levels in the study.The data indicate that AV-101 had good bioavailability and a favorable PK profile.

"The primary safety and tolerability endpoints of the Phase 1 program were met.This is a very safe compound with no observed side effects," commented Mark S. Wallace, MD, Chair of the Division of Pain Medicine, Department of Anesthesiology at UCSD and the principal investigator of the study."AV-101 is an exciting prodrug compound that acts through a promising mechanism to treat pain.I am excited to move this compound into Phase 2 studies for the treatment of pain."

About AV-101

Aimed at multi-billion dollar neurological disease and disorders and depression markets, AV-101, also known as "L-4-chlorokynurenine" (4-Cl-KYN), is a novel, orally available prodrug that is converted in the brain into an active metabolite, 7-chlorokynurenic acid (7-Cl-KYNA), which regulates an important neurotransmitter in the brain called the N-methyl-D-aspartate (or NMDA) receptor.A synthetic analogue of kynurenic acid, a naturally occurring neural regulatory compound, 7-Cl-KYNA is one of the most potent and selective blockers of the regulatory GlyB-site of the NMDA receptor.

VistaGen's AV-101 IND application covers clinical development for neuropathic pain. In addition to neuropathic pain, VistaGen expects the results of its Phase 1 clinical program to be useful for supporting the development of AV-101 for other neurological disorders including depression and epilepsy.

About VistaGen Therapeutics

VistaGen is a biotechnology company applying human pluripotent stem cell technology for drug rescue, predictive toxicology and drug metabolism screening. VistaGen's drug rescue activities combine its human pluripotent stem cell technology platform, Human Clinical Trials in a Test Tube, with modern medicinal chemistry to generate novel, safer chemical variants (Drug Rescue Variants) of once-promising small molecule drug candidates. These are drug candidates discontinued by pharmaceutical companies, the U.S. National Institutes of Health (NIH) or university laboratories, after substantial investment in discovery and development, due to heart or liver toxicity or metabolism issues. VistaGen uses its pluripotent stem cell technology to generate early indications, or predictions, of how humans will ultimately respond to new drug candidates before they are ever tested in humans, bringing human biology to the front end of the drug development process.

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Vistagen Therapeutics Successfully Completes Final Phase 1 Safety Study of AV-101

Tuning stem cell fate: Researchers uncover epigenetic mechanisms of embryonic stem cell pluripotency and differentiation

Jan. 22, 2013 The research group of Luciano Di Croce, from the Center for Genomic Regulation (CRG) in Barcelona (Spain), has discovered that RYBP and CBX7, two proteins essential for gene regulation, are at the heart of the most critical decision faced by embryonic stem cells: what type of cells to become. These findings, published in the last issue of Cell Reports, shed light on the molecular mechanisms involved in stem cell biology and might have important therapeutic implications.

Stem cells are the precursors of our tissue and organs. Using them could be highly promising for regenerative medicine, yet little is known about the mechanisms that regulated the potential of stem cells to give rise to the different cell types within organisms.

The Polycomb repressive complex 1 (PRC1) is an epigenetic regulator essential for stem cell function and cancer progression. It has only recently become clear that PRC1 comes in different flavors, depending on which specific proteins are incorporated into it (such as either CBX7 or RYBP). However, whether or not these PRC1 subtypes carry out different biological functions was unclear. This work, headed by Lluis Morey in the Di Croce group, has taken an important step in clarifying this question.

Using the most advanced sequencing technology, Di Croce and his coworkers analyzed 2.64 billion DNA nucleotides from mouse embryonic stem cells to determine which regions are controlled by PRC1-RYBP as compared to PRC1-CBX7. Both complexes shared some biological functions. Surprisingly, however, the two complex subtypes also performed distinct functions. We were able to show that these two complex subtypes can have different roles, with one involved more in metabolism and the other more in development, commented Morey.

Understanding the extent to which the different PCR1 subtypes carry out the critical decisions that determine cell fate presents the next large goal. We are lucky to be able to address these questions within a network of experts in our European FP7 4DCellFate project, since we believe that the answers will be important for understanding how to implement stem cells into therapeutic applications, stated Di Croce.

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Tuning stem cell fate: Researchers uncover epigenetic mechanisms of embryonic stem cell pluripotency and differentiation

Stem Cell Joint Repair Treatment Osteoarthritis Cartilage in Bangkok, Thailand

Food and Healthcare Press Releases Monday January 21, 2013

Bangkok--21 Jan--Urban Beauty Thailand

Osteoarthritis is the most common form of arthritis. It causes pain, swelling and reduced motion in your joints. It can occur in any joint, but usually affects your hands, knee, hips or spine. Thailand Osteoarthritis breaks down the cartilage in your joints. Cartilage is the slippery tissue that covers the ends of bones in a joint. Healthy cartilage absorbs the shock of movement. When you lose cartilage, your bones rub together. Over time, this rubbing can permanently damage the joint. Factors that may cause osteoarthritis include:

Being overweight

Getting older

Injuring a joint

Thailand Osteoarthritis, or OA, is often related to aging, although sometimes the cause is not known. Before the age of 55 it occurs equally in women and men. After that age it is more common in women. By the age of 70 the majority of people will have at least minor Osteoarthritis.

Stem cell treatment in Thailand is one of the best options to get rid of osteoarthritis. Like many other procedures osteoarthritis treatment in Thailand uses autologous adult stem cells. These are harnessed from the patients fat cells so there is very little chance of patients body rejecting them.

Adipose (fat) tissue extraction tends to be more worthwhile than other methods such as bone marrow extraction. This is because it produces up to ten times more stem cells. Adipose derived stem cells (ASCs) have been shown to be just as effective as other stem cells as they display proliferative efficiency and multipotency in tissue regeneration.

Stem cell treatment in Bangkok uses new technology known as Adistem Cell Technology. Photoactivation Technology has been used for activating adipose derived stem cells (ASCs) for therapeutic and regenerative application since 2008. This technology uses low intensity of light at specific frequencies to increase various anti-inflammatory and healing agents from ASCs. Harvesting ASCs is done through a simple, minimally invasive liposuction under local anesthesia. The process is relatively easy and painless and poses minimal risk to the patient. It is a single procedure in a sterile setting. After harvesting, the stem cells are separated from the fats using standard technique.

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Stem Cell Joint Repair Treatment Osteoarthritis Cartilage in Bangkok, Thailand

'Brimming with energy' after $20K stem cell treatment

Jennifer Vasilakos got the shocking surprise of her life after helping a man who stopped to ask her for directions. That man happened to be the billionaire founder of the Beanie Baby company and what he did may have saved her life. NBC's Kristen Dahlgren reports.

By Kristen Dahlgren and Erica Ayisi, NBC News

What started out as a modest fundraising event held in a Santa Barbara, Calif., parking lot has turned into a life-changing moment for Jennifer Vasilakos, thanks to a chance meeting with Beanie Baby billionaire Ty Warner.

It all began ina parking lot in July of last year. Vasilakos, 42, set up a table near her hometown's annual Santa Barbara French Festival to raise money for stem cell treatment, displaying signs and flyers that explained her cause.She also brought a small moneybox to stash cash made from parking cars for festival-goers.

Equipped with sunglasses, a water bottle and coffee, Vasilakos was prepared to spend the day raising awareness and telling people her personal story that she was diagnosed with acute renal failure in 2011 and had received dialysis three times a day, three times a week. It was a grueling regimen that she would endure the rest of her life. A kidney transplant wasnt an option; she had been rejected as a candidate because of a previous bout with cancer.

Vasilakos, aReiki teacher and herbalist,decided her only option was to save up for stem cell treatment a costly procedure that is not performed in the United States.

But as the day wore on, her moneybox largely remained empty. The festival, she said, was completely dead.

That's when a lost driver in a small little car drove up, looking for directions. Jennifer chatted him up.

Louis Lanzano / ASSOCIATED PRESS

Ty Warner, Beanie Baby creator and chief executive of Ty Inc., arrives at the Toy Fair to sign

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'Brimming with energy' after $20K stem cell treatment

Drug targets hard-to-reach leukemia stem cells responsible for relapses

Jan. 17, 2013 Researchers at the University of California, San Diego School of Medicine have discovered that hard-to-reach, drug-resistant leukemia stem cells (LSCs) that overexpress multiple pro-survival protein forms are sensitive -- and thus vulnerable -- to a novel cancer stem cell-targeting drug currently under development.

The findings, published in the January 17 online issue of Cell Stem Cell, open the possibility that diseases like chronic myeloid leukemia (CML) and some solid tumor cancers might -- in combination with other therapies -- be more effectively treated with this drug, and with a lower chance of relapse.

Led by principal investigator Catriona H. M. Jamieson, MD, PhD, associate professor of medicine and director of stem cell research at UC San Diego Moores Cancer Center, the researchers found that a compound called sabutoclax appears to selectively target LSCs that express particular protein isoforms through alternatively splicing, a fundamental process in which a gene is able to code for multiple proteins.

An emerging class of drugs called tyrosine kinase inhibitors (TKI) -- such as imitinib (Gleevec), gifitinib (Iressa) and sunitinib (Sutent) -- has become a popular anti-cancer treatment. However, current TKIs are not 100 percent effective. In cases of CML, for example, some LSCs tucked protectively within bone marrow elude destruction, develop resistance to therapy, self-renew and eventually cause the leukemia to dramatically return.

Jamieson and colleagues found that alternative splicing of BCL2 genes, which code for proteins involved in apoptosis or programmed cell death, specifically promoted malignant transformation of dormant white blood cell precursors into "blast crisis" LSCs. The blast crisis is the final phase of CML when overabundant, abnormal white blood cells crowd out healthy cells, causing serious dysfunction.

Of clinical importance, they noted that sabutoclax, which suppresses all BCL2 anti-apoptotic proteins, renders these marrow-dwelling blast crisis LSCs sensitive -- and more susceptible -- to TKI-based therapeutics at doses that do not harm normal progenitor cells.

"Our findings show that pan-BCL2 inhibition will be critical for the eradication of cancer stem cells in CML and that there is an essential link between cancer stem cell dormancy, pro-survival BCL2 isoform expression and therapeutic resistance," Jamieson said. "By using a novel pan-BCL2 inhibitor, we may be able to prevent therapeutic resistance by sensitizing malignant stem cell clones to TKIs."

The findings may have implications for treating solid tumor cancers, such as colon, prostate, breast, and brain cancers, noted Daniel J. Goff, the study's first author. "With many of these tumor types being shown to harbor cancer stem cells, it raises the question of whether BCL2 family expression as well as isoform-switching may be crucial for the maintenance of cancer stem cells in these diseases as well," he said. "If so, they may also be candidates for treatment with a BCL2 inhibitor like sabutoclax."

Co-authors are Angela Court Recart, Anil Sadarangani, Heather Leu, Janine Low-Marchelli, Wenxue Ma, Alice Y. Shih, Ifat Geron, Minya Pu, Lei Bao, Ryan Chuang, Larisa Balaian, Peggy Wentworth, Kristen M. Smith, Christina A.M. Jamieson, Sheldon R. Rorris and Karen Messer, UCSD Department of Medicine and UCSD Moores Cancer Center; Hye-Jung Chun and Marco Marra, Michael Smith Genome Sciences Center, Vancouver, BC, Canada; Christian L. Barrett and Kelly A. Frazer, UCSD Department of Pediatrics; Maryla Krajewska, Jun Wei, Dayong Zhai, Maurizio Pellecchia and John C. Reed, Sanford-Burnham Medical Research Institute; Jason Gotlib, Stanford Medical Center; Mark Minden, Princess Margaret Hospital, Toronto, Canada; Giovanni Martinelli, Institute of Hematology and Medical Oncology, University of Bologna, Italy; Jessica Rusert and Lawrence S.B. Goldstein, UCSD Department of Cellular and Molecular Medicine and Howard Hughes Medical Institute; Kim-Hien Dao, Oregon Health and Science University, Portland; Kamran Shazand and Thomas J. Hudson, Ontario Institute for Cancer Research, Toronto, Canada.

Funding for this research was provided by a California Institute for Regenerative Medicine (CIRM) early Translational II grant (TR2-1789), a CIRM HALT leukemia disease team grant (DR1-01430), the UCSD CIRM Training Grant (TG2-01154), the Ratner Family Foundation, the National Cancer Institute (CA-55164), the National Institutes of Health (CA-149668), the Ontario Institute for Cancer Research, Genome Canada, Ontario Genomics Institute and the Canadian Institute of Health Research.

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Drug targets hard-to-reach leukemia stem cells responsible for relapses

Scots scientists make stem cell breakthrough

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Helen Puttick Health Correspondent

The Edinburgh University team discovered the bacteria, which cause leprosy, convert cells in the nerve system so they become like stem cells.

These cells are known as the building blocks of life and are seen as the key to finding cures for a range of conditions from motor neurone disease to spinal cord injuries, which are currently irreversible.

It is hoped scientists will be able to use leprosy bacteria to grow stem cells, which have the ability to turn into any other type of cell needed by the body. These could then be transplanted into patients to repair damage.

Dr Rob Buckle, head of regenerative medicine at the Medical Research Council, has described the research as "groundbreaking".

He said: "This discovery is important not just for our understanding and treatment of bacterial disease but for the rapidly progressing field of regenerative medicine.

"In future, this knowledge may help scientists to improve the safety and utility of lab-produced pluripotent stem cells and help drive the development of new regenerative therapies for a range of human diseases, which are currently impossible to treat."

Longer-term he is hopeful the insight will lead to a new way of creating stem cell therapies. The cells can be harvested from embryos but this raises ethical issues and Mr Rambukkana said there was also a danger of embryonic stem cells developing into tumours. The leprosy cells do not carry this risk.

Mr Rambukkana said: "This (research) is very intriguing as it is the first time we have seen that functional adult tissue cells can be reprogrammed into stem cells by natural bacterial infection, which also does not carry the risk of creating tumorous cells.

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Scots scientists make stem cell breakthrough

Bacteria's hidden skill could pave way for stem cell treatments

Jan. 17, 2013 A discovery about the way in which bugs spread throughout the body could help to develop stem cell treatments.

Researchers at the University of Edinburgh have found that bacteria are able to change the make-up of supporting cells within the nerve system, called Schwann cells, so that they take on the properties of stem cells.

Because stem cells can develop into any of the different cell types in the body -- including liver and brain cells -- mimicking this process could aid research into a range of degenerative conditions.

Scientists made the discovery studying bacteria that cause leprosy, which is an infectious neurodegenerative disease. The study, carried out in mice, found that in the early stages of infection, the bacteria were able to protect themselves from the body's immune system by hiding in Schwann cells or glial cells.

Once the infection was fully established, the bacteria were able to convert the Schwann cells to become like stem cells.

Like typical stem cells, these cells were pluripotent, meaning they could then become other cell types, for instance muscle cells. This enabled the bacteria to spread to tissues in the body.

The bacteria-generated stem cells also have another unexpected characteristic. They can secrete specialised proteins -- called chemokines -- that attract immune cells, which in turn pick up the bacteria and spread the infection.

Scientists believe these mechanisms, used by leprosy bacteria, could exist in other infectious diseases.

Knowledge of this newly discovered tactic used by bacteria to spread infection could help research to improve treatments and earlier diagnosis of infectious diseases.

The study is published in the journal Cell.

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Bacteria's hidden skill could pave way for stem cell treatments

A Dangerous Game: Some Athletes Risk Untested Stem Cell Treatments

Image: Peter Ryan

In 2005, at the age of 32, then Los Angeles Angel Bartolo Coln won the American League Cy Young Award for best pitcher, one of professional baseball's top honors. He stumbled through subsequent seasons, however, after a series of rips and strains in the tendons and ligaments of his throwing arm, shoulder and back. In 2009 he all but quit baseball. Desperate to reclaim his career, Coln flew home to the Dominican Republic in 2010 for an experimental procedure not vetted or approved by the U.S. Food and Drug Administration. Doctors centrifuged samples of Coln's bone marrow and fat, skimmed off a slurry containing a particular kind of stem cellimmature, self-renewing cells that can turn into a variety of tissuesand injected it into his injured shoulder and elbow. Within months of the procedure the then 37-year-old Coln was once again pitching near the top of his game for the New York Yankeescommanding a 93-mile-per-hour fastball.

Whether the injected stem cells rejuvenated his arm is an open question. The fda and the International Society for Stem Cell Research warn that no rigorous studies have demonstrated that such treatments safely and effectively repair damaged connective tissue in people. The results of related animal studies, though promising, have raised more questions than answers. The term stem cell makes it sound cutting edge and exciting, says Paul Knoepfler, a cell biologist at the University of California, Davis, who also writes frequently on policy surrounding stem cells. But the role of these cells in sports medicine is essentially all hype.

No matter, apparently, to the aging, injured athletes who have followed Coln's lead. Lefty pitcher C. J. Nitkowski, who underwent the same procedure in 2011, told readers of his personal blog that he did not mind the lack of carefully controlled research. My attitude is I don't have the time to wait for the five- or 10-year study to come out, the then 38-year-old relief pitcher wrote, so I'm taking a chance now. Besides, Nitkowski figured, even if the treatment did not work, any health risks ought to be slight because the cells involved were his own.

That might not be such a safe bet. Numerous studies suggest that Coln, Nitkowski and others trying untested stem cell treatments may be risking more than they think. Even a syringe of one's own stem cells taken from one part of the body and squirted into another may multiply, form tumors, or may leave the site you put them in and migrate somewhere else the fda warns on its Web site. More clinical research is needed to define safety procedures, as well as how many cells of which types and what other tissue factors produce the desired results. In some animal studies, for example, the regenerated tissue is not as strong or flexible as the original. In other cases, an overgrowth of scar tissue makes the injected tendon or ligament adhere to the overlying skin. By preventing different tissues from gracefully sliding past one another, these adhesions sometimes pull an even bigger tear in an already serious wound.

In addition, Knoepfler worries that high-profile sports testimonials by Coln, Nitkowski and others will encourage joggers with blown-out knees and the parents of sore-armed Little Leaguers to demand the procedure before it has been thoroughly tested. When celebrities take to a new treatment, many other people follow suit, he says. Such premature enthusiasmor an unforeseen tragedy that results from proceeding too fast too sooncould also prevent serious researchers from getting funding to do the kinds of careful experiments that might eventually lead to safe and reliable treatments.

Seeds of Repair

The need for better ways to reknit damaged tendons and ligaments is painfully apparent to the roughly two million Americans in a given year who seek medical help for tears in their shoulder's rotator cuff, for example, or the 100,000 patients in the same year who undergo surgery in the U.S. to repair a ripped or ruptured anterior cruciate ligament (ACL) of the knee. Tendons and ligaments are tough, fibrous bands, made mostly of collagen, that anchor networks of muscles to a bone or link bones and cartilage across crucial joints. They lend strength, flexibility and stability to your daily twists and turns, whether you are rocketing a baseball across home plate or hefting a suitcase into an overhead bin. Once frayed or snapped, they can take many months or longer to mendeven with surgery.

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A Dangerous Game: Some Athletes Risk Untested Stem Cell Treatments

Body fat good source of stem cells, say doctors

By Philip C. Tubeza Philippine Daily Inquirer

Health Secretary Enrique Ona said that the Department of Health would come out in the coming weeks with the rules to regulate stem cell therapy in the country. INQUIRER FILE PHOTO

MANILA, PhilippinesHealth buffs may abhor body fat but it is actually a good source for stem cells that can be used to help treat diseases ranging from athritis, diabetes, or even HIV/AIDS in the future, according to a stem cell expert.

Speaking at the first national convention of the Philippine Society for Stem Cell Medicine, Vasilis Paspaliaris, a stem cell expert from Greece, said body fat or adipose tissues have been proven to be rich sources of mesenchyme stem cells, used for regenerative medicine.

Why fat? Whats the interest in fat? Theres a lot more mesenchyme stem cells in adipose tissue, Paspaliaris said during the convention at the Manila Hotel.

Many of you cosmetic surgeons know that fat has been used as a filler for breast enhancements. Everyone knew there was a therapeutic use for fat. And plastic surgeons were quite aware of it. They have seen its rejuvenative effects, he added.

He said that while mesenchyme tissues could also be found in the skin and the kidneys, there is 10,000 times more mesancyme stem cells in adipose tissue.

And what is a big deal in adipose tissue is that (its) easily accessible with a minimal invasive procedure. More importantly, we can take a little amount of fat and we already have enough numbers of cells that we can take back straight to our patients, he added.

However, Paspaliaris said that the fat person would not necessarily have more mesenchyme stem cells than someone thinner.

The bigger you are does not mean that you have more stem cells. It just means you have more lipids (or stored energy), he added.

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Body fat good source of stem cells, say doctors

Stem Cell Therapy Guidelines Readied

MANILA, Philippines --- The Department of Health (DOH) is preparing guidelines for the use of stem cell therapy in the treatment of diseases in the Philippines.

This was announced by DOH Secretary Enrique T. Ona yesterday in a convention on stem cell therapy at the Manila Hotel.

Ona said a bio-ethics advisory board will develop the guidelines which will include ethical standards in the application of stem cell therapy to treat diseases such as malignancies, blood disorders and metabolic disorders, among others.

"The institutional board will review and approve Stem Cell therapies based on guidelines by the advisory board," Ona said.

He added that the board will also include ethical and legal issues surrounding stem cell therapy.

Last week, the Philippine Medical Association (PMA) and the Philippine Society for Stem Cell Medicine (PSSCM) issued a joint statement that warned against the dangers of receiving stem cell transplants that came from another source other than the patient's body.

"If the stem cell that you received is not from your own body, it could lead to fatal complications," Philippine Society for Stem Cell Medicine (PSSCM) and the PMA said.

The doctors warned that complications arising from stem cell transplants include graft-versus-host disease, stem cell (graft) failure, organ injury, infections, cataracts, infertility, new cancers, and even death.

Ona said a public hearing will be held on January 18 regarding the preliminary draft of the guidelines.

He said the guidelines will ensure the minimum quality of service and application in the use of stem cells in health settings.

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Stem Cell Therapy Guidelines Readied