An international team of researchers has reported improvement in three patients with multiple sclerosis (MS), all of whom received autologous adult stem cell therapy in which the stem cells were derived from each patient’s own adipose (fat) tissue.

Entitled, “Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis”, the publication appears today in the Journal of Translational Medicine. In the article, the scientists describe important properties of the “stromal vascular fraction” (SVF), which not only is rich in mesenchymal stem cells (MSCs) but also contains high concentrations of other beneficial constituents such as T-regulatory cells, endothelial precursor cells, preadipocytes, and a type of anti-inflammatory macrophage known as “alternatively activated” (M2) macrophage, which is a cell type with both anti-inflammatory and immunomodulatory properties. As the authors of the article explain, MSCs are already known to “produce numerous neurotrophic growth factors and inhibit pathological inflammation”, while “alternatively activated macrophages and T-regulatory cells are speculated to have the ability to modify the innate and adaptive immune responses”. One of the most important points of the paper, therefore, is not merely the potency of the adult stem cells – the MSCs – that were used, but also the degree to which immunomodulatory agents from the SVF are involved in the repair and healing processes. To be precise, therefore, the scientists who conducted the study are referring to the therapy as “SVF therapy”, rather than simply as “adult stem cell therapy”, since more components comprise the therapy than adult stem cells alone.

In MS, the two main conditions that contribute to the progression of the disease are the body’s autoimmune attack against the central nervous system, and the resulting demyelination. Currently, there is no standard medical treatment that can address either problem adequately, yet this study would seem to indicate that SVF therapy is capable of accomplishing both objectives, namely, SVF therapy seems to be capable of inhibiting the autoimmune attack against the central nervous system, and SVF therapy seems to remyelinate the demyelinated neurons.

In particular, the paper describes 3 patients with MS, all of whom went into remission following administration of the autologous, non-expanded, adipose-derived cells. Dr. Boris Minev, of the Moores Cancer Center and the Division of Neurosurgery in the Department of Medicine at the University of California at San Diego, is one of the leading investigators of the study. As Dr. Minev explains, , “All 3 patients in our study showed dramatic improvement in their condition after the course of SVF therapy. While obviously no conclusions in terms of therapeutic efficacy can be drawn from these reports, this first clinical use of fat stem cells for the treatment of MS supports further investigations into this very simple and easily-implementable treatment methodology. None of the presently available MS treatments selectively inhibit the immune attack against the nervous system, nor do they stimulate regeneration of previously damaged tissue. We’ve shown that SVF cells may fill this therapeutic gap.”

Significantly, one of the patients had suffered frequent and painful seizures (over 600 seizures) for three years prior to receiving the treatment, yet after receiving the SVF therapy his seizures stopped completely. He also reported a reduction in spasticity in his arms and legs as well as improved cognition. The second patient reported improved balance, coordination, mood and energy level following the therapy. Perhaps most dramatically, the third patient had first been diagnosed with MS over 15 years ago, in 1993, and within a matter of weeks after receiving the SVF therapy in 2008 he reported significant improvement in his balance, gait and coordination. According to Dr. Minev, “His condition continued to improve over the next few months and he is currently reporting a continuing improvement and ability to jog, run and even bicycle.”

The therapy consists of a very simple procedure which begins with a liposuction for removing cells from the patient’s adipose (fat) tissue, after which the cellular components of the fat are purified, in particular, the component known as the “stromal vascular fraction” (SVF). The purified SVF is then readministered to the patient intravenously. Such a simple procedure could be easily be conducted virtually anywhere. In fact, this very same liposuction procedure is already performed in thousands of plastic surgery clinics worldwide. A number of commercial entities are currently developing bench-top closed systems precisely for this type of autologous adipose cell therapy, such as the Celution system developed by Cytori Therapeutics and the TGI 1000 platform that is being developed by Tissue Genesis Inc., and both of which are currently entering clinical trials.

Adipose tissue is already known to contain a high concentration of adult stem cells, primarily mesenchymal stem cells (MSCs), in even larger quantities than bone marrow. MSCs are excellent candidates for an MS therapy for two main reasons, namely, 1/ MSCs have been shown in animal models to repair damaged neurons and to regenerate lost myelin, and 2/ MSCs suppress inflammatory reactions and produce different factors that slow inflammation. The SVF is thus a particularly robust form of therapy not merely for its rich abundance of MSCs but also because of its high concentrations of T-regulatory cells, which suppress autoimmunity, and also because of the large populations of the “alternatively activated” macrophage. In any type of MS therapy, it is absolutely essential not just to repair damaged neurological tissue but also to address the underlying mechanisms of autoimmunity through immune modulation. SVF appears to do both.

Autologous fat-derived MSC therapy has already been administered to over 3,500 horses and over 1,500 dogs for different types of inflammatory and autoimmune conditions as well as bone and joint injuries, without adverse side effects, thru the biotech company Vet-Stem, whose founder and CEO, Dr. Robert Harman, is one of the scientists involved in this MS study and one of the authors of this paper. As Dr. Minev adds, “Our collaborator in this publication, Dr. Robert Harman, CEO of Vet-Stem, has treated over 3,500 horses and 1,500 dogs with fat-derived stem cells for inflammatory conditions such as osteoarthritis immune-mediated polyarthritis. The current work is an excellent example of veterinary findings being translated into human medicine.”

In fact, as the authors point out in their abstract, “Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose-derived MSCs. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn’s fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported.”

Given the dramatic improvement achieved in all 3 MS patients, the authors of the paper conclude by proposing that larger, controlled trials be conducted.

According to Dr. Thomas Ichim, CEO of Medistem and one of the authors of the paper, “In addition to our endometrial regenerative cell (ERC) universal donor stem cell technology, for which an IND (investigational new drug appllication) has been filed, Medistem has been committed to developing a pipeline of therapeutic products, including in the area of immune modulation. Given our previous observations and IP (intellectual property) filings that a stem cell-rich component of adipose tissue, called the stromal vascular fraction, can concurrently immune-modulate while inducing regenerative activities, we are pleased to see the clinical translation of this approach into multiple sclerosis patients.”

Medistem Inc. is a biotechnology company founded to develop and commercialize technologies related to adult stem cell extraction, manipulation, and use for treating inflammatory and degenerative diseases. The company’s lead product, the endometrial regenerative cell (ERC), is a “universal donor” stem cell derived from menstrual blood that possesses the ability to differentiate into nine tissue types and produce large quantities of growth factors while exhibiting a large proliferative capacity. The company is currently focusing on the use of endometrial regenerative cells for the treatment of critical limb ischemia, an advanced form of peripheral artery disease that causes approximately 160,000 amputations in the U.S. per year.

The Journal of Translational Medicine is an open access journal of BioMed Central.

Scientists in the Departments of Anatomy and Neurology at the School of Medicine and Public Health at the University of Wisconsin at Madison have reported the successful formation of oligodendrocytes from human embryonic stem cells (hESCs), with a few surprising discoveries.

Within the human central nervous system (CNS), oligodendrocytes are the neuroglia that are responsible for forming myelin, which is the dielectric, electrically insulating fatty sheath that covers the axons of neurons throughout the entire body, and which is essential for the transmission of electrical signals along nerve fibers. While Schwann cells supply myelin to the axons of peripheral nerves, oligodendrocytes supply myelin exclusively to the axons of the CNS, and several demyelinating diseases such as, most notably, multiple sclerosis, are a result of the deterioration of the myelin that ordinarily is found within the CNS. Although degenerative conditions such as multiple sclerosis are known as “demyelinating” diseases, the problem is primarily with the oligodendrocytes, and secondarily with the myelin. Since myelin is approximately 80% lipid and 20% protein, nutrition is also known to play a crucial role in the maintenance of healthy myelin.

In the past, laboratory researchers have encountered a number of frustrating difficulties when trying to coax hESCs into oligodendrocytes, despite the fact that it has always been relatively easy to differentiate oligodendrocytes from mouse ESCs (mESCs). In mice, the production of oligodendrocytes is accomplished by exposure of the mESCs to a protein known as “sonic hedgehog homolog” (SHH), a ligand in the murine signaling pathway and a morphogen that has been well described in the regulation of vertebrate organogenesis and neurological organization. In hESCs, however, exposure to SHH was not enough to generate oligodendrocytes. As an aside, it is interesting to note that a number of scientists and clinicians alike continue to criticize the name of this homolog, which is an evolution of the original “hedgehog” gene that was first discovered in Drosophila melanogaster (the fruit fly) and which resulted in pointed projections that formed on the surface of Drosophila embryos whenever the gene was absent or inactivated, thereby resembling a hedgehog appearance in the embryos, which thus inspired the name. For discovering the hedgehog gene, Drs. Eric Wieschaus, Christiane Nusslein-Volhard and Edward B. Lewis were awarded the 1995 Nobel Prize in Physiology or Medicine. Currently 3 proteins have been identified in the mammalian “hedgehog” family, the other 2 besides SHH being “desert hedgehog” (DHH) and Indian hedgehog (IHH).

Now, Dr. Su-Chun Zhang and his colleagues at the University of Wisconsin at Madison may have discovered some of the reasons for the difficulties that scientists have typically encountered when trying to differentiate oligodendrocytes from hESCs. Among other things, the scientists found that exposure of the hESCs to SHH will, in fact, still result in the differentiation of the hESCs into oligodendrocytes, even though the differentiation process requires 14 weeks for hESCs as opposed to merely 2 weeks with mESCs. Paradoxically, however, one of the growth factors that promotes the differentiation of mESCs into oligodendrocytes, namesly, Fgf2 (fibroblast growth factor 2, also known as “basic fibroblast growth factor”, one of the 22 members of the structurally signaling molecules that comprise the FGF family), was surprisngly found to inhibit the differentiation in hESCs. Although Fgf2 has been known to play a key role in keeping hESCs in an undifferentiated state, the precise mechanisms by which this occurs have not yet been elucidated, nor is it understood exactly how Fgf2 promotes differentiation in mESCs.

As Dr. Zhang explains, “This was quite a surprise given that this is exactly how we direct mouse ESCs to become oligodendrocytes. But we have discovered an unexpected twist in the cell’s response to the same external factor. It nevertheless explains why so many research groups have failed to persuade human neural stem cells to become oligodendrocytes for the past decade.”

Dr. Zhang adds, “We are now able to generate a relatively enriched population of oligodendrocyte precursor cells that may be used to repair lost myelin sheaths. These findings also raise awareness of the direct translatability of animal studies to human biology. In this regard, the human oligodendrocytes generated from human ESCs of disease-induced pluripotent stem cells can provide a useful tool in the future for screening pharmaceuticals directly on human cells.”

Given the complexities inherent in the differentiation process from hESCs, and the uncertainties that still remain in controlling this process, it is therefore all the more impressive that other doctors and scientists, in studies unrelated to that of Dr. Zhang’s, have already achieved significant improvement in human multiple sclerosis patients using adult, not embryonic, stem cells. (Please see the related article on this website, entitled, “Adult Stem Cells From Fat Help Multiple Sclerosis Patients”, dated April 24, 2009, as reported in the Journal of Translational Medicine).

Indeed, with numerous patients throughout the world who need treatment now, today – not ten years from now, nor even one year from now, nor even one month from now – the need for a viable clinical stem cell therapy for diseases and injuries grows increasingly urgent. While discoveries such as Dr. Zhang’s are extremely interesting from a scientific point of view, they offer little that is immediately translatable to the clinic, from a therapeutic point of view. For medical therapies that are already being used in real clinics by real doctors on real human patients with real human diseases, today, at this very moment, adult stem cells are the only stem cells that already constitute any type of clinical therapy.

Researchers have published the results of a study demonstrating both the safety and the feasibility of an adult stem cell therapy for the treatment of both acute and chronic spinal cord injuries.

Scientists at the California-based company, DaVinci Biosciences, in collaboration with the Luis Vernaza Hospital in Ecuador, have conducted a clinical study in which 8 patients were treated with autologous (in which the donor and recipient are the same person) adult stem cells derived from each patient’s own bone marrow. The stem cells were then administered via a proprietary “multiple route delivery technique” to the 8 patients, 4 of whom suffered from acute spinal cord injuries and 4 of whom suffered from chronic spinal cord injuries. The routes of administration included delivery directly into the spinal cord, directly into the spinal canal and intravenously. Throughout the 2-year follow-up period, all 8 patients were observed to improve through the measurement of such parameters as regained mobility and sensation, regained bladder control and confirmation by sequential MRIs of actual morphological regeneration within the spinal cord itself. No adverse side effects were observed.

Approximately 400,000 people in the U.S. alone are estimated to suffer from spinal cord injuries, with approximately 11,000 new cases diagnosed each year. On average, 52% of all spinal cord injuries result in paraplegia while around 47% result in quadriplegia. According to Dr. Rafael Gonzalez, director of R&D for DaVinci Biosciences, “We are pleased to see the publication of our research. It represents a giant step in the process of improving the quality of life in people living with spinal cord injury and other neurodegenerative disorders.”

According to Francisco Silva, president of DaVinci Biosciences, “The outcome of this study is exciting for us and our patients. We plan on expanding and building upon the results. We strongly believe that this is an important first step for realizing the therapeutic application of stem cells for treating diseases and injuries such as spinal cord injury in humans.”

As Dr. Paul Sanberg, director of the Center of Excellence for Aging and Brain Repair at the University of South Florida, adds, “Although there have been numerous studies in animals demonstrating the benefits of stem cell treatment for spinal cord injury, this is the first published study of its kind. It gives patients the possibility that their quality of life can be improved.”

Headquartered in Costa Mesa, California, DaVinci Biosciences has additional facilities throughout North and South America and is involved in a number of parnerships with universities, medical research institutions and hospitals. DaVinci’s primary area of development is focused on cell-based therapeutics and small molecule compounds in the treatment of neurodegenerative disorders such as spinal cord injury, multiple sclerosis, Parkinson’s disease, and ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease). In collaboration with one of its partners, the company has patented a surgical technique for the effective delivery of cell-based therapies directly into the spinal cord. DaVinci Biosciences is divided into 2 main business units which include DV Biologics, the main research division, and DV Therapeutics, the development division which advances the molecular and cell-based technologies to therapeutic applications.

In the exploding field of regenerative medicine, this new study provides strong evidence that autologous adult stem cells derived from bone marrow offer a safe and feasible therapy which improves the quality of life for patients suffering from acute and chronic spinal cord injury.

Once again, the biotech company Opexa Therapeutics announces strong preclinical data for its proprietary diabetes therapy, developed from autologous adult stem cells. The new study demonstrates that adult stem cells harvested from the mononuclear cells of peripheral blood are differentiable into pancreatic-like cells, which mimic the morphology and function of the beta islet cell clusters of the pancreas in their ability to secrete insulin, glucagon and somatostatin, as well as in the expression of pancreatic and endocrine-specific biomarkers and in the high levels of C-peptide, a byproduct of insulin synthesis.

Derived from both healthy and diabetic subjects, the mononuclear cells have yielded strong in vitro as well as in vivo data in animal studies, and further preclinical studies will be conducted for the determination of optimal dosing, delivery, route-of-administration and toxicology. As Opexa advances toward a Phase I clinical trial, primary endpoints for which have already been identified, a protocol for the clinical trial has also already been established in consultation with the FDA and Opexa’s Clinical Advisory Board.

According to Neil K. Warma, president and CEO of Opexa, “I am pleased to see important advances with our stem cell therapy as this technology could offer benefits not only for the treatment of diabetes but also in other disease areas. We are also hopeful to be able to derive one course of treatment from a single blood draw from a diabetic patient which, ideally, would lead to a readily available source of patient-specific beta-cells suitable for autologous cell transplantation.”

As Donna Rill, senior vice president of Operations, adds, “We have developed a manufacturing process based on a small-scale, bag-based system which we believe should yield significant cost savings over typical embryonic stem cell and cadaveric cell manufacturing processes. We have extensive experience with cell therapy technology, having just completed a 150 patient Phase IIb clinical study with our T-cell therapy and we have applied many of the same principles to our stem cell manufacturing process. Much work still remains but we are encouraged with these data.”

Opexa Therapeutics is focused on the development and commercialization of patient-specific autologous cellular therapies for the treatment of autoimmune diseases such as multiple sclerosis and diabetes. In the treatment of multiple sclerosis, Opexa has already achieved excellent results with its lead product candidate, Tovaxin, which is a novel T-cell vaccine that is specifically tailored to each patient’s disease profile and which has recently completed Phase IIb clinical trials. Opexa holds the exclusive worldwide license for the technology that allows the derivation of adult multipotent stem cells from the mononuclear cells of peripheral blood, and which in turn makes possible the large-scale efficient production of monocyte-derived stem cells, without the risk of immune rejection. (Please see the related news article on this website, entitled, “Opexa to Present Data on its Cellular Therapies for Autoimmune Diseases”, dated November 10, 2008, and originally reported in The Wall Street Journal, for more information on Tovaxin).

Opexa therapeutics deals exclusively with adult stem cells, not embryonic stem cells.

In Mid Cheshire, England, young women with toddlers are being taught to consider their children’s teeth as a form of family “medical insurance”. For £950 (approximately 1,400 U.S. dollars), the company Bio-Eden will store a tooth’s soft pulp, which contains a plentiful amount of adult stem cells that have already been shown to differentiate into a wide variety of tissue types, and which can be used in the future, if necessary, not only to treat the individual from whom the tooth originated but also blood-relatives of that individual.

Bio-Eden supplies participating mothers with a collection kit that includes storage containers and cooling packs for children’s teeth, which parents are instructed to collect as soon as the teeth fall out. If the proper collection containers are not immediately available, the mothers are encouraged to store the teeth in fresh milk in the refrigerator until the teeth can be sent to Bio-Eden along with the appropriate collection supples. According to Vanessa Weeks, sales manager of Bio-Eden, “The process is simple and easy, it is non-invasive and allows you to use something that is normally discarded. The mums are wowed by the possibilities.”

Once the teeth are sent to Bio-Eden, the soft pulp is then divided and stored simultaneously at two separate physical locations. As Ms. Weeks explains, “It means that, in the unlikely event of a major physical threat at our lab, there will still be another sample available.”

Adult stem cells harvested from dental pulp have been shown to differentiate into a diverse range of tissue types which include, most notably, neurological tissue. As such, dental pulp-derived adult stem cells are believed to constitute an excellent source of stem cell therapies that could be used in the treatment of conditions such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, traumatic brain injury and spinal cord injury, among others. (Please see the related news article on this website, entitled, “Brain Tissue Formed From Monkey Teeth Stem Cells”, dated November 12, 2008, and first reported in the journal Stem Cells).

During the sixth week of embryonic development, human deciduous teeth begin forming in utero from the dental lamina which is a band of epithelial tissue that develops from the ectoderm, the outermost germ layer from which cells and tissues of the nervous system also develop. Hence, it is hardly surprisng that adult stem cells which are present in dental pulp are easily differentiable into neurological tissue. Since the outer part of the integumentary system including the epidermis also develops from the ectoderm, it is also not surprising that dental pulp stem cells have been found to develop into a number of cell types that compose these tissues as well. Interestingly, dental pulp has also been found to contain a variety of cell types from the mesoderm, which include chondrocytes (which are found in cartilage and which produce and maintain the cartilaginous matrix), osteoblasts (which are responsible for bone formation), adipocytes (fat cells) and mesenchymal stem cells (highly potent adult stem cells that are also found in bone marrow and umbilical cord blood). Dental pulp stem cells are therefore also believed to be useful as therapies in the treatment of heart disease, diabetes and in the reconstruction of damaged bones and joints, among other ailments. Indeed, the full range of therapies to which dental pulp-derived adult stem cells may be applicable is potentially unlimited.

Even though Bio-Eden is a U.S. company, headquartered in Austin, Texas, Bio-Eden has international laboratories in the U.K. and Thailand which provide services throughout Europe and Asia. Additional sites are currently be planned for Russia, India, Australia and the Middle East.

Bio-Eden is the first company to collect, harvest and cryogenically store adult stem cells that are extracted from deciduous teeth, also known as baby teeth. Bio-Eden is registered with and approved by the U.S. FDA.

As Bio-Eden states on the homepage of their website, next to a picture of a nurse with wings, “One day, the Tooth Fairy could save your child’s life.”

Citing a number of examples which demonstrate the “markedly diminished need for expanding these cell lines for either patient therapy or basic research”, Bernardine Healy, M.D., explains in clear and logical terms why embryonic stem cells are obsolete.

According to Dr. Healy’s article in U.S. News and World Report, “Even for strong backers of embryonic stem cell research, the decision is no longer as self-evident as it was, because there is markedly diminished need for expanding these cell lines for either patient therapy or basic research. In fact, during the first six weeks of Obama’s term, several events reinforced the notion that embryonic stem cells, once thought to hold the cure for Alzheimer’s, Parkinson’s, and diabetes, are obsolete. The most sobering: a report from Israel published in PLoS Medicine in late February that shows embryonic stem cells injected into patients can cause disabling if not deadly tumors.”

As Dr. Healy further explains, “The report describes a young boy with a fatal neuromuscular disease called ataxia telangiectasia, who was treated with embryonic stem cells. Within four years, he developed headaches and was found to have multiple tumors in his brain and spinal cord that genetically matched the female embryos used in his therapy.” (Please see the related news article on this website, entitled, “Fetal Stem Cell Therapy Could Prove Fatal”, dated February 17, 2009).

Such findings should make everyone rethink, among other things, Geron’s upcoming clinical trials with human embryonic stem cells, and Dr. Healy even suggests that the U.S. FDA (Food and Drug Administration) should reconsider the wisdom of having granted such authorization in the first place. According to Dr. Healy, “His experience [the Israeli boy who developed the tumors] is neither an anomaly nor a surprise, but one feared by many scientists. These still-mysterious cell creations have been removed from the highly ordered environment of a fast-growing embryo, after all. Though they are tamed in a petri dish to be disciplined, mature cells, research in animals has shown repeatedly that sometimes the injected cells run wildly out of control – dashing hopes of tiny, human embryos benignly spinning off stem cells to save grown-ups, without risk or concern. That dream was still alive only a few weeks before this report. Within days of Obama’s inauguration, the Food and Drug Administration approved its first-ever embryonic stem cell study in humans: the biotech company Geron’s plan to inject highly purified human embryonic cells into eight to 10 patients with acute spinal cord injuries. (The cells are from a stem cell line approved by Bush because it predated his ban). The FDA should now be compelled to take another look: Are eight to 10 patients enough, or one year of monitoring sufficient, to assess safety? And doctors who participate in the trial will have to ask what every doctor must ask before performing research on a human subject: Were I this patient, would I participate? Would I encourage my loved ones to do so?”

In acknowledging the extraordinary successes that have already been accomplished with adult stem cells, Dr. Healy adds, “Even as the future of embryonic stem cells has dimmed, adult stem cell research has scored major wins evident just in the past few months. These advances involve human stem cells that are not derived from human embryos. In fact, adult stem cells, which occur in small quantities in organs throughout the body for natural growth and repair, have become stars despite great skepticism early on. … Such stem cells can be removed almost as easily as drawing a unit of blood, and they have been used successfully for years in bone marrow transplants. To date, most of the stem cell triumphs that the public hears about involve the infusion of adult stem cells. We’ve just recently seen separate research reports of patients with spinal cord injury and multiple sclerosis benefiting from adult stem cell therapy.”

Even iPS (induced pluripotent stem) cells, which are also not without their own dangers, are more promising than embryonic stem cells, and on this topic Dr. Healy cites not only the inherent medical risks of iPS cells but also the advice of the first scientist who ever isolated an embryonic stem cell, the famous Dr. James Thomson. As Dr. Healy describes, “While these cells [iPS cells] might become a choice for patient therapy in time, scientists are playing this down for now. Why? These embryonic-like cells also come with the risk of cancer. James Thomson, the stem cell pioneer from the University of Wisconsin who was the first to grow human embryonic stem cells in 1998, is an independent codiscoverer of iPS cells along with Japanese scientists. Already these reprogrammed cells have eclipsed the value of those harvested from embryos, he has said, because of significantly lower cost, ease of production, and genetic identity with the patient. They also bring unique application to medical and pharmaceutical research, because cells cultivated from patients with certain diseases readily become laboratory models for developing and testing therapy.”

Finally, Dr. Healy points out another important distinction which is often overlooked, namely, the distinction between the simple act of overturning President Bush’s restriction on the use of federal funding for human embryonic stem cell research, which President Obama has promised to do, and the far more difficult task of repealing the Dickey-Wicker Amendment, which became law under the Clinton Administration and which forbids both the creation and the destruction of embryos for scientific research. In regard to this matter, Dr. Healy has this to say: “The importance of stem cells for medical research has never been greater, and the scientific and public clamor for unimpeded research is fully understandable. But it’s important that Obama and everyone supporting a lifting of the ban be clear with the public on what is involved in this decision; it’s more complex than advertised. The more ethically charged decision – less understood by the public and one Congress has avoided – involves the ban on creating human embryos in the laboratory solely for research purposes. In fact, President Clinton is the one who balked at allowing scientists to use government money for embryo creation and research on stem cells harvested from such embryos; Bush only affirmed the Clinton ban. The scientific community has been able to attract nonfederal money for such work, and it is going on all the time in stem cell institutes. Scientists want relief from the inconvenience and expense of keeping that work and the money that supports it separate from federal dollars. Reversing the Executive Orders of 2 prior presidents on embryo creation, which even the Congress has been unwilling to tackle, is a far bigger issue than lifting the ban on the use of IVF embryos slated for destruction. Obama stands for transparency, and it’s important for him to make sure the public understands his decision, including that all stem cells are not the same or created equally.”

Dr. Bernardine Healy, a cardiologist who has spent more than 25 years practicing medicine, is currently a senior writer and health editor for U.S. News and World Report, and the author of the magazine’s “On Health” column. A graduate of Harvard Medical School, she was one of only ten women out of a class of 120 Harvard Medical School students at that time. She is a former Professor of Medicine at Johns Hopkins University School of Medicine where she was also Director of the Coronary Care Unit and Assistant Dean for Post-Doctoral Programs and Faculty Development. She has served in the capacity of Presidential Advisor under several administrations, beginning in 1984 when President Reagan appointed her as Deputy Director of the White House Office of Science and Technology Policy. In 1991, President George H.W. Bush appointed her as the first woman Director of the National Institues of Health, and in the George W. Bush administration she was appointed in 2001 to the President’s Council of Advisors on Science and Technology where she served as an advisor on bio-terrorism. Additionally, she was President of the American Heart Association from 1998 to 1999, and President and CEO of the American Red Cross from 1999 to 2001, during which time she led the response of the American Red Cross to the terrorist attacks of September 11th, 2001, which included the creation of a $200 million family grant program for the families of victims and the initiation of a stratetic blood reserve from extra blood collections, among other programs. From 1995 to 1999 she was Professor of Medicine and Dean of the College of Medicine and Public Health at Ohio State University. She has written 2 books and coauthored more than 220 peer-reviewed manuscripts on cardiovascular research and health science policy. Despite her numerous administrative, executive and Presidential appointments, from which she became known for her outspoken and innovative policy-making decisions, she has continued to treat patients throughout much of her career. She has also served as a medical correspondent for CBS news.

After participating in a small clinical trial at Northwestern University, Edwin McClure seems to have recovered from multiple sclerosis (MS). Conducted on 21 participants and led by Dr. Richard Burt, the clinical trial involved treating the MS patients with their own adult stem cells. The only drawback of the study, however, was the use of chemotherapy to destroy each patient’s immune system prior to the adult stem cell therapy. Nevertheless, patients such as Mr. McClure have shown dramatic improvement.

Diagnosed with MS four years ago at the age of 18, Edwin McClure underwent a regimen of conventional MS medication but without any results. According to Mr. McClure, “I would get fatigued. I couldn’t deal with the heat. I had really bad balance.” Then he heard about the trial being conducted at Northwestern University in Chicago, and decided to participate. Now, he says, “I really don’t feel like I have multiple sclerosis anymore.” In regard to the chemotherapy, however, he adds, “It was rough.”

Approximately 400,000 people in the U.S. and 2.5 million people globally are estimated to suffer from MS, which is a degenerative, autoimmune, demyelinating disease of the central nervous system, the precise causes of which remain unknown, and a precise cure for which has not previously existed. According to Dr. Burt, however, “Well now for the first time in battling MS, I think you can say there’s a study that’s shown we’ve turned the tide against the disease.”

In actuality, other doctors have already had success in treating patients with multiple sclerosis, but without the brutal and deliberate destruction of the immune system with radiation. As previously reported on this website, prior to receiving the autologous stem cell transplantation in the clinical trial led by Dr. Burt, each patient also underwent immunological myeloablation, in which radiation is employed to destroy the patient’s immune system. While such a procedure had previously been considered a necessary part of the therapy, even though it exposes the patient to potentially life-threatening risks, today an increasing number of doctors are questioning the logic and necessity of subjecting their patients to deliberate immune destruction, and with valid scientific reason. In a publication that appeared over two years ago, in the Journal of Translational Medicine in January of 2007, Dr. Neil H. Riordan et al. posed the following question: “…in patients who are not suffering from a disease that is associated with an aberrant bone marrow such as hematological malignancies or immunological dysfunctions, how is it justifiable to subject them to the high levels of morbidity and mortality associated with immune suppression?” Dr. Riordan and his team of scientists then examined compelling evidence which strongly indicates that pre-transplant immune suppression is unnecessary for many types of autologous hematopoietic cell therapies and even for some allogeneic therapies that utilize “universal donor” cells such as mesenchymal stem cells and the CD34+ stem cells that are found in umbilical cord blood, and for which immune rejection is not even a concern. As Dr. Riordan and his colleagues wrote in their 2007 paper in a section that is subtitled, “Mesenchymal stem cells do not need myeloablation for efficacy”: “Currently there are several ongoing clinical trials in Phase I-III using ‘universal donor’ mesenchymal stem cells in non-conditioned recipients of Crohn’s disease, GVHD (graft-versus-host disease) and myocardial infarction. Although these cells are bone marrow expanded mesenchymal cells, the superior proliferative potential of cord blood mesenchymal cells may allow them not only to escape immune destruction, but also to expand in vivo and mediate therapeutic effects superior to those derived from bone marrow. The fact that regulatory agencies have allowed advancement of ‘off-the-shelf’ universal donor mesenchymal stem cells supports the numerous reports of clinical efficacy in an allogeneic setting.”

Nevertheless, for clinical trials such as those conducted by Dr. Burt at Northwestern University, the adult stem cell therapy offers tangible improvement – at least for those patients who survive the life-threatening destruction of their immune systems from radiation. One can only conclude, therefore, as has already been demonstrated by other doctors at other clinics, that patients would exhibit even greater and faster improvement if they did not have to recover from the deliberate destruction of their immune systems prior to receiving the stem cell therapy, and also if the stem cell therapy would utilize the “superior proliferative potential” of the “immune privileged” adult stem cells that are found in umbilical cord blood.

Edwin McClure and his mother, Bernice, were featured today on the Early Show with CBS television correspondent Debbye Turner Bell.

Physicians at Northwestern University in Chicago have reported dramatic improvement in patients who were treated with adult bone marrow stem cells for multiple sclerosis (MS). Led by Dr. Richard Burt, the doctors treated eleven women and ten men who had had MS for approximately 5 years but who were still in the early stages of the relapsing-remitting form of the disease, and who had been unresponsive to conventional medical treatment. The adult stem cell therapy consisted of autologous hematopoietic stem cells that were extracted from each patient’s own bone marrow, and follow-up monitoring of the patients was conducted for 3 years.

The adult stem cell therapy was found to halt, and in some cases even reverse, the progression of the disease. Although all of the 21 patients who participated in the clinical trial improved, 17 patients exhibited improvement that was measurable by one point or more on a standardized disability scale, which is considered to be a statistically significant improvement. MRI scans and other imaging techniques showed that remyelination had occurred, and further testing revealed that the stem cell therapy had “cleansed” the immune system of defective white blood cells.

The study confirms similar results obtained by doctors Gianluigi Mancardi and Riccardo Saccardi at the University of Genoa in Italy earlier last year.

Approximately 400,000 people in the U.S. alone have been diagnosed with various forms of MS, which is an autoimmune disease that is characterized by progressive neurological degeneration and which has previously been considered incurable.

Prior to receiving the autologous stem cell transplantation in the clinical trial led by Dr. Burt, each patient also underwent immunological myeloablation, in which radiation is employed to destroy the patient’s immune system. While such a procedure has previously been considered a necessary part of the therapy, even though it exposes the patient to potentially life-threatening risks, today an increasing number of doctors are questioning the logic and necessity of subjecting their patients to deliberate immune destruction. In a publication that appeared in the Journal of Translational Medicine in January of 2007, Dr. Neil H. Riordan et al. posed the following question: “…in patients who are not suffering from a disease that is associated with an aberrant bone marrow such as hematological malignancies or immunological dysfunctions, how is it justifiable to subject them to the high levels of morbidity and mortality associated with immune suppression?” Dr. Riordan and his team of scientists then examined compelling evidence which strongly indicates that pre-transplant immune suppression is unnecessary for many types of autologous hematopoietic cell therapies and even for some allogeneic therapies that utilize “universal donor” cells such as mesenchymal stem cells and the CD34+ stem cells that are found in umbilical cord blood. As Dr. Riordan and his colleagues wrote in their 2007 paper in a section that is subtitled, “Mesenchymal stem cells do not need myeloablation for efficacy”: “Currently there are several ongoing clinical trials in Phase I-III using ‘universal donor’ mesenchymal stem cells in non-conditioned recipients of Crohn’s disease, GVHD (graft-versus-host disease) and myocardial infarction. Although these cells are bone marrow expanded mesenchymal cells, the superior proliferative potential of cord blood mesenchymal cells may allow them not only to escape immune destruction, but also to expand in vivo and mediate therapeutic effects superior to those derived from bone marrow. The fact that regulatory agencies have allowed advancement of ‘off-the-shelf’ universal donor mesenchymal stem cells supports the numerous reports of clinical efficacy in an allogeneic setting.”

Nevertheless, as Dr. Burt and his colleagues at Northwestern University have reported, their adult stem cell procedure, even though it was preceded by the systematic destruction of each patient’s immune system, “not only seems to prevent neurological progression but also appears to reverse neurological disability” in multiple sclerosis, and the results “imply that this is a valuable alternative to the transplant conditioning therapies used so far.”

One can only conclude, therefore, that patients would exhibit even greater improvement if they did not have to recover from the deliberate and life-threatening destruction of their immune systems prior to receiving the stem cell therapy, and also if the stem cell therapy would utilize the “superior proliferative potential” of the “immune privileged” adult stem cells that are found in umbilical cord blood.

The Texas-based stem cell company Opexa Therapeutics, Inc., which is focused on the development of patient-specific cellular therapies for the treatment of autoimmune diseases such as multiple sclerosis and diabetes, today offered a corporate update to its employees, shareholders and the general public.

Perhaps most notable on the list of topics to be addressed was the TERMS (Tovaxin for Early Relapsing Multiple Sclerosis) study that commenced in October of 2008, and which is a Phase IIb multi-center, randomized, double-blind placebo-controlled clinical trial in which 150 patients with the relapsing-remitting form of multiple sclerosis were treated with Tovaxin. The primary efficacy endpoint will measure the “Cumulative number of gadolinium-Enhanced brain Lesions” (CELs) via MRI scans at 28, 36, 44 and 52 weeks, while secondary efficacy endpoints will measure annualized relapse rare (ARR) and new CELs at weeks 28 through 52, as well as the T2-weighted lesion volume when compared to the baseline. Although a comprehensive analysis of the study will be conducted over the next several months, initial data collected thus far are encouraging.

Additionally, a number of discussions are ongoing for various partnerships between Opexa and other companies, such as for the further development of its lead therapy, Tovaxin, as well as of other novel therapies for the treatment for multiple sclerosis, with the anticipation of pivotal trials and future commercialization. A number of possible partnerships are also currently in discussion for the development and commercialization of Opexa’s stem cell therapy to treat Types 1 and 2 diabetes, such as its monocyte-derived stem cells (MDSCs) and monocyte derived pancreatic-like islets (MDI) as a potential therapeutic transplantation product in the treatment of diabetes. Additionally, Opexa has developed proprietary in vitro processes for the derivation of MDSCs from blood monocytes which are then expanded ex vivo and converted to MDI for transplantation into the hepatic main portal vein of diabetic patients. Currently, there is a strong emphasis at Opexa for the further development of MDSC technology as a platform for autologous transplantation therapy in the treatment of diabetic patients via the ex vivo generation of MDIs. Unlike most multipotent stem cells, MDSCs exhibit a specific time-dependent expression of markers that distinguish them from other cells, and which have been shown to differentiate into hematopoietic, epithelial, endothelial, endocrine and neuronal cells.

According to Dr. Dawn McGuire, a neurologist and member of Opexa’s Clinical Advisory Board, “Tovaxin offers the potential for immunomodulatory treatment that is exquisitely individualized for a complex disease that manifests in a highly individual manner. Early results with Tovaxin suggest reduction not only in relapse rates but also in global neuronal loss among patients with the most active disease. I see great promise here.”

Opexa also announced the resignation of COO Dr. Jim Williams, effective February 13, 2009, after which time Dr. Williams will remain actively involved with Opexa in a consulting capacity. According to Neil Warma, president and CEO of Opexa Therapeutics, “With possibly the safest therapy for MS demonstrated to date and some very encouraging efficacy data in clinically relevant relapse rates and disability scores, we are pleased with the level of discussions we are having with potential partners. We are extremely fortunate to have someone of Dr. McGuire’s experience to further advise on our clinical development strategy and steward the clinical development of Tovaxin. Her substantial knowledge and experience in MS, having overseen the early development of Tysabri, will certainly contribute very favorably to our development program and partnering discussions. We are grateful to Jim for having contributed immensely to the development of Tovaxin to date and for overseeing the management of the first-in-class TERMS IIb study and we are pleased he will remain a consultant to the company as we continue forward with our clinical strategy.”

An individualized T-cell therapeutic vaccine which combats the characteristic demyelination of nerve fibers in the central nervous systems of people with multiple sclerosis, Tovaxin consists of attenuated patient-specific myelin-reactive T-cells against peptides of proteins from myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP) or combinations thereof.

Tovaxin’s dual mechanism of action has been shown to exhibit, on the one hand, an anti-idiotypic effect which induces an immune response that depletes and regulates the circulating pathogenic myelin-reactive T-cells that attack the myelin sheath of nerve fibers, and, on the other hand, an anti-ergotypic effect which rebalances the overall immune system by causing a shift from pathogenic inflammatory T-cells to anti-inflammatory T-cells.

Mary Posta suffers from an advanced form of multiple
sclerosis termed