The Japanese biotech company, JCR Pharmaceuticals, has announced that it has begun clinical trials for the treatment of graft-versus-host disease (GVHD) with its proprietary product, known as JR-031, which consists of a patented preparation of human mesenchymal stem cells derived from bone marrow.

GVHD is a common and potentially fatal complication of allogeneic (in which the donor and recipient are not the same person) bone marrow transplantation, for which a reliable cure has not previously existed. Conventional treatments with corticosteroids which are intended to induce T-cell immune suppression carry a high risk of infection and cancer relapse. Now, however, adult stem cells offer the first actual therapy which has already been shown to halt and reverse GVHD, without imparting further dangers and risks to the patient.

JR-031 uses adult stem cell technology originally developed by the U.S. company Osiris Therapeutics, which is currently in Phase III clinical trials with its human mesenchymal stem cell products in Europe and the U.S., where the therapy has received Fast Track designation from the corresponding regulatory agencies for the treatment of GVHD. In Japan, where Phase I and II clinical trials will be conducted at more than ten hospitals, JCR Pharmaceuticals is developing the therapy in collaboration with the Mochida Pharmaceutical Company. Some patients have already been treated with JR-031, and data should be available within the next few months. If Japan’s Ministry of Health approves JR-031, as expected, this mesenchymal stem cell product will then become the first stem cell-based therapy in Japan. In anticipation of successful clinical trials in Japan, as already demonstrated by the success of clinical trials conducted by Osiris in the U.S. and Europe, JCR Pharmaceuticals and Mochida have already entered into a formal agreement in which both companies will co-develop and commercialize JR-031 for Japan.

JCR Pharmaceuticals is focused on the R&D of human-derived bioactive substances, especially enzyme-, hormone-, and cell-based therapies for orphan diseases. The company was founded in 1975 and is based in Ashiya City, Japan. It is traded on the Osaka Stock Exchange under the symbol JCRPF.

Zoey, the 14-year-old American Eskimo dog, used to suffer from advanced arthritis of the hip, but found no improvement with pharmaceuticals, and hip surgery was contraindicated by his advanced age. Fortunately, however, Zoey’s owner followed the advice of Zoey’s veterinarian, and now Zoey’s hip and quality of life have both significantly improved, thanks to canine adult stem cell therapy.

According to Zoey’s owner, Raymond Walsh, “It did wonders. He is having another round. But had we not given the first shot back in August we might have had to put him under.”

Since Vet-Stem began marketing their services last year, they have now treated more than 1,500 dogs and cats with autologous adult stem cells, extracted from each animal’s own fat. The procedure is quick, simple, minimally invasive, safe, highly effective, and while it is not cheap, it is less expensive than conventional surgical and pharmaceutical therapies which may not be effective at all. The first stem cell extraction and transplant typically run between $2,500 and $3,500, although the second transplant will often cost much less since extraction is only necessary once. In Zoey’s case, additional injections of his own stem cells cost $350 each. As his owner Raymond puts it, “If it prolongs his life, it was worth it.” The entire stem cell extraction procedure consists of the approximate equivalent of 2 or 3 tablespoons of the animal’s own adipose tissue (fat) which is surgically removed under anesthesia and shipped overnight to Vet-Stem’s laboratories in southern California where the stem cells are isolated, expanded and returned two days later to the veterinarian who injects the stem cells back into the animal. Not only do the stem cells automatically target the injured tissue, but they also stimulate endogenous stem cells which in turn are mobilized into action and participate in the healing and repair process. Although improvements are usually dramatic and immediate, even after the first injection, additional injections may be necessary, depending upon the age and condition of the animal. Very few animals ever need more than a total or 2 or 3 treatments, however, before they are fully restored to their natural, pain-free state of mobility – which contrasts sharply with conventional therapies such as most prescription medications which may need to be taken indefinitely, without ever producing any tangible signs of improvement and while even possibly causing further damage to the animal through dangerous side effects and other associated risks.

Success stories are common in the field of veterinary medicine with this type of stem cell therapy, which utilizes exclusively adult stem cells, not embryonic stem cells, since embryonic stem cells are notoriously problematic and carry a number of dangerous risks, both in humans and in animals, not the least of which is the formation of teratomas (tumors).

Another success story involved the 7-year-old golden retriever named Daisy who, in the summer of last year, received the same type of autologous adult stem cell procedure as did Zoey, at which time adult stem cells derived from Daisy’s own fat were injected into both of her hind legs. Although she had previously been unable to walk at all on her left hind leg, she was restored to effortless and painless mobility following the stem cell treatment. According to her owner, Mary Benik, “She is back to what she was. Before, she had been holding her foot up, favoring it. I hope it continues to work because I have bad knees and I would do it if it could help me.”

In fact, Vet-Stem’s consistent success is becoming increasingly difficult for the human medical profession to ignore, and pioneering patients such Zoey and Daisy are now inspiring similar therapies for humans. According to the CEO of Vet-Stem, Dr. Bob Harman, “When you look at a labrador retriever with arthritis in his hips, that is the same disease that you and I have. Fractures are similar too, even though they are four-legged.”

Indeed, Vet-Stem is now working with the San Diego company Cytori Therapeutics which is harvesting adult stem cells from human adipose tissue for reconstructive breast surgery following a masectomy, by utilizing a proprietary device that has already been approved for use with breast cancer patients in Europe. According to Tom Baker, director of investor relations at Cytori, “Our first application is taking the cells out and combining them with fat to allow fat to be used as a natural filler in breast reconstruction.” Although this is just one example of a very specific application of adult stem cell technology, other applications extend throughout the vast spectrum of degenerative diseases and traumatic injuries, including those of orthopedic, cardiovascular, neurological and immunological origin, in which there is no shortage of companies that have already demonstrated impressive results in human clinical trials, such as, most notably, the adult stem cell company Osiris Therapeutics, among others.

Once again, in a symbiotic relationship that can trace its origins back throughout the millennia, it is unclear today exactly who is training whom, and who is really helping whom, in the ongoing mutual advancement and enlightenment of homo sapiens and our canine companions.

After isolation and in vitro expansion over several months of autologous neural stem cells that had been obtained from cortical and subcortical tissue samples of a patient during neurosurgical procedures, the neural stem cells were then carefully examined for safety, function and differentiation. It was not until nine months after harvesting of the cells that the researchers administered unilateral microinjections of the autologous cell suspensions containing differentiated dopaminergic and GABAergic neurons into the brain of a patient with advanced Parkinson’s disease. Since the cells were autologous (in which the donor and recipient are the same person), there was no need for immunosuppression.

According to Dr. Michel Levesque, the lead author of the study and a physician at Cedars-Sinai Medical Center as well as the UCLA School of Medicine and the Brain Research Institute at UCLA, “We have documented the first successful adult neural stem cell transplantation to reverse the effects of Parkinson’s disease, and we have also demonstrated the long term safety and therapeutic effects of this approach.”

He adds, “Of particular note are the striking results this study yielded. For the 5 years following the procedure, the patient’s motor skills improved by over 80% for at least 36 months.”

Parkinson’s disease is a neurological disorder in which impaired neurons located within the substantia nigra region of the brain are no longer able to produce dopamine, the chemical that is necessary for natural muscle movement and coordination throughout the body. In the U.S. alone, approximately 1.5 million people have already been diagnosed with the disease and approximately 60,000 new cases of Parkinson’s disease are diagnosed each year. While Parkinson’s usually develops after the age of 65, approximately 15% of all people with the disease are under the age of 50. Conventional pharmacological treatments which attempt to replace or mimic dopamine may mask the symptoms of the disease, but none have been able to reverse the progression of the disease. Additionally, side effects, contraindications and other risks associated with such drugs are a serious concern.

Now, however, as Dr. Levesque has demonstrated, adult stem cell therapy offers the first type of treatment for Parkinson’s which actually reverses the progression of the disease, safely and effectively.

Presumably not yet aware of the medical scandal caused by the fetal stem cell therapy that resulted in the development of a tumor in an Israeli boy (see the related news article on this website entitled “Fetal Stem Cell Therapy Could Prove Fatal”, dated February 17, 2009), the authors of this study nevertheless felt it important to compare their autologous adult stem cell therapy with therapies that use fetal or embryonic tissue, which, the authors point out, “carry inherent risks of immunological reactions, infectious transmission and intractable dyskinesias, in addition to serious ethical concerns”, not to mention also the risk of tumor formation. By sharp contrast, autologous adult stem cell therapy does not pose any such risks, and thereby offers a new cellular therapeutic alternative to diseases of the central nervous system, especially for the selective neural repair of discrete cell loss in progressive degenerative diseases such as Parkinson’s.

As the authors conclude in their publication, “Adult neural stem cells derived from a patient’s cerebral tissue can become a source of differentiated neurons, useful for grafting in the treatment of Parkinson’s disease. The combined GABAergic and dopaminergic cells produced a long lasting motor improvement. This approach has the potential to make neural stem cell therapy acceptable and available to a large number of patients.”

For the average high school sophomore, learning to drive is a big deal. For 16-year-old Macie Morse, who just earned her learner’s permit and is now quite proficient behind the wheel of a car, the achievement is one that neither she nor anyone else in her family had ever thought would be possible. According to Macie, “It was one of the most exciting times of my entire 16 years.”

Having been born blind, until the age of 15 Macie had 20/4,000 vision in one eye and only light perception in the other eye. A visual score of 20/4,000 means that at a distance of 20 feet the person can see objects with as much clarity and visual acuity as the average person can see from a distance of 4,000 feet. The particular visual defect from which Macie suffered was optic nerve hypoplasia, which is an underdevelopment of the nerve that transmits visual signals from the eye to the brain. Unable even to read unless the print was within inches of her eye, Macie could only dream of participating fully in the world around her. As Macie puts it, “I’ve always wondered what it would be like to lay on the couch and watch TV. I always wondered what it would be like to see my friends.” According to Dr. James Thompson, optometrist and owner of Advanced Eye Care in Fort Collins, “If the optic nerve isn’t healthy, glasses aren’t going to do anything for anybody.”

Now, after having received adult stem cell therapy, Maci has 20/80 vision in one eye and 20/400 vision in the other, which is improved to 20/30 vision with a monocle.

Prior to Macie, only 10 other people had ever undergone the adult stem cell procedure for optic nerve hypoplasia, which costs $40,000, not counting travel expenses to and from the clinic in China where the therapy is administered. Raising money through a variety of sources throughout their local community, Macie and her mother were able to travel to China together so that Macie could have the therapy. Almost immediately, Macie showed dramatic improvement.

Legally, in order to be allowed to drive, one must have a minimum of 20/40 vision, a requirement which Macie now meets. According to her mother, “Before, I was always one step behind her, keeping an eye on her. Now I can let her be free. She’s going to be fine.”

Researchers have announced a new and somewhat surprising discovery with the novel population of extremely promising adult stem cells known as endometrial regenerative cells (ERCs). Already recognized for their highly angiogenic properties, ERCs are currently in development as a treatment for critical limb ischemia, which is an advanced form of peripheral artery disease. Now, in a counter-intuitive turn of events, ERCs have also demonstrated a strong ability to inhibit angiogenesis in tumor growth.

ERCs share certain similarities with mesenchymal stem cells while also exhibiting unique surface markers, and the cells are highly superior in a number of characteristics such as growth factor production, differentiability and expandability. In this latest study, researchers examined the ability of unmanipulated ERCs to influence gliomal growth in a Sprague Dawley rat model. A glioma is a type of cancer that arises from glial cells and is therefore most commonly found in the brain though also less often in the spine.

In a paper entitled, “Inhabition of Intracranial Glioma Growth by Endometrial Regenerative Cells”, the scientists found that ERCs inhibit the growth of these types of tumors. In fact, regardless of the route of administration, the ERCs were observed to induce dramatic inhibition of the glioma, with a 49% reduction in volume after intravenous administration of the ERCs and a 46% reduction in volume following intratumoral administration. In both cases, both an inhibition of angiogenesis as well as a reduction in the number of CD133+ cells were associated with the diminished intracranial tumor growth.

Such findings suggest a number of intriguing possibilities, such as, for example, an association between the strong anti-inflammatory properties of ERCs and the conceptual model of cancer in which tumor stem cells are thought to be triggered to enter the cell cycle as a result of cellular injury, which usually precipitates an inflammatory response. Although the precise molecular mechanisms underlying the behavior of ERCs have yet to be fully elucidated, they nevertheless offer a number of new and promising therapeutic modalities.

As the authors explain in their paper, “Despite the angiogenic potential of ERCs in the hindlimb ischemia model, these data support a paradoxical tumor inhibitory activity of ERCs. Further studies are needed to determine the qualitative differences between physiological angiogenesis, which seems to be supported by ERCs, and tumor angiogenesis which appeared to be inhibited.”

The embryonic stem cell company Geron is not allowed to enter the European market due to a questionable patent.

The European Patent Office has upheld an earlier decision to reject a patent application for the use of embryonic stem cells as filed by the Wisconsin Alumni Research Foundation in 1995. When Dr. James Thomson of the University of Wisconsin at Madison became the first person to isolate an embryonic stem cell in the late 1990s, much of his funding came from the Geron Corporation. Consequently, today Geron holds the worldwide license for the technology developed by Dr. Thomson and his colleagues.

In its response to the European Patent Office decision, Geron filed a form with the U.S. Securities and Exchange Commission (SEC) on Friday in which the company claims that “the applicability of this decision to such lines is uncertain.”

Geron has recently dominated the news because of the authorization that it has received from the U.S. FDA to begin the first clinical trials ever to be conducted with human embryonic stem cells. The clinical trials willl test the company’s product, known as GRNOPC1, which consists of live human embryonic stem cells, in the treatment of spinal cord injuries. The purpose of Phase I clinical trials is to test safety, whereas efficacy tests will be conducted later in subsequent clinical trials, assuming that safety can be proven, although this remains the subject of widespread speculation.

The SEC filing follows a secondary stock offering by the company on Thursday, at which time Geron conducted what investors are calling a “conveniently timed” public offering, after the close of the stock markets, of 7.25 million shares at $6.60 per share, significantly below Thursday’s closing price of $7.77 per share. The 12% discount grossed Geron approximately $43 million. Following the public offering, Geron is now in a goverment-mandated quiet period, during which time it is not allowed to speak to the press.

In the U.S., a number of unanswered questions remain in regard to Geron’s upcoming clinical trial. Geron will not even be able to begin enrolling patients in its small Phase I clinical trial until the summer of 2009, since the company has not yet received final clearance from the hospitals in which the trial will be conducted. Only ten patients will participate in the trial, but Geron is required to wait a full month between each patient due to the serious safety concerns that are associated with embryonic stem cells. Assuming that Geron will be able to enroll one patient per month – an assumption which has been questioned by many experts in the field – the study will not be fully enrolled until the middle of 2010 at the earliest. Additionally, since Geron must complete a full year of treatment for each patient, data will not be available until 2011. A number of investors have shorted Geron’s stock, having lost confidence in the company as a consequence of the years that it devoted to cancer vaccines and to telomerase-based drugs with no tangible results to show for the effort, two prime examples of which were Geron’s prostate cancer vaccine which dominated the news in 2003 and which has long since been buried and forgotten, in addition to Geron’s telomerase-inhibitor cancer drug known as GRN163L which seemed promising in 2007 and which temporarily drove up the stock price, but which ultimately yielded only disappointing data.

Geron’s stock plummeted 16.7%, or $1.30, to $6.47 during midday trading on Friday.