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

Celgene Cellular Therapeutics (CCT), a wholly owned subsidiary of Celgene Corporation, announced today that the U.S. Food and Drug Administration (FDA) has approved the company’s investigational new drug application to initiate a clinical trial which will test PDA001, an immunomodulatory therapeutic agent that utilizes adult stem cells derived from human placental blood via a proprietary process. Phase I of the clinical process will begin in the U.S. by the end of 2008, in which a multi-center trial will test the therapy on patients with moderate-to-severe Crohn’s disease who have also been found to be refractory to oral corticosteroids such as prednisone and to the immune suppressants that are commonly prescribed for such conditions.

PDA001 is a proprietary placental-derived adult stem cell therapy which is scalable to traditional pharmaceutical levels and which has applications that include immunology, inflammation, hematology and oncology. CCT owns and has patented a variety of proprietary technologies that are directed to novel placental cell types and cell populations, including methods for collecting, processing and storing many types of stem cells from the placenta. PDA001 is the first product to be developed as a result of CCT’s expanding portfolio.

According to Dr. Lloyd F. Mayer, director of the Immunology Institute, professor of medicine and chief of the divisions of clinical immunology and gastroenterology at Mt. Sinai Hospital in New York City, “This first placental-derived stem cell clinical trial is of vital importance given the significant number of people suffering from this debilitating disease. With the positive results from in vivo biodistribution and safety studies, our hope is that PDA001 will suppress the atypical immune and inflammatory reactions involved in the pathogenesis of Crohn’s disease, thereby resulting in a decrease in symptoms and improved quality of life for patients.”

Currently nearly a million people in the U.S. alone suffer from Crohn’s disease, which is a chronic inflammatory condition of the gastrointestinal tract that can be fatal in extreme cases. In the past, conventional medical treatment has consisted of non-specific anti-inflammatory or immunosuppressive agents, none of which are reliably effective and most of which cause side effects which are intolerable in a high percentage of the patients.

According to Robert Hariri, M.D., Ph.D., who is also CEO of Celgene Cellular Therapeutics, “This is the first step in our program to initiate clinical evaluations in a range of indications including not only Crohn’s disease, but other serious inflammatory and autoimmune diseases, such as multiple sclerosis and rheumatological disorders as well. By creating a novel cell therapy from a readily available source that does not require human leukocyte antigen-matching, we are hopeful that we can treat a large number of patients with a variety of devastating diseases.”

Celgene Cellular Therapeutics (CCT) is an adult stem cell company the focus of which is the discovery and development of novel therapeutics based upon adult stem cells derived from human placental and umbilical cord blood. In particular, the human placenta-derived cell therapy known as PDA001 is a cellular immune modulatory agent comprised of a novel cell population that is expanded in culture after being derived from normal, healthy, full-term human placental tissue. PDA001 is known to be genetically stable, displaying a normal diploid chromosome count, normal karyotype and normal senescence after prolonged in vitro culture exposure. Additionally, PDA001 is capable of immunomodulation and has been found to suppress T-cell proliferation while exhibiting immunomodulatory effects on other cell types that are involved in the immune response such as T-cell subsets, macrophages and dendritic cells.

As the first ever to be conducted with placental-derived stem cells, these clinical trials not only represent a milestone in the treatment of Chron’s disease, but also in the therapeutic advancement and availability of this particularly versatile population of adult stem cells.

The biotech company Opexa announced today that its president and CEO, Neil K. Warma, will deliver a corporate presentation of its patient-specific therapies that are targeted for the treatment of autoimmune diseases such as multiple sclerosis (MS) and diabetes. The presentation will be at Rodman & Renshaw’s 10th Annual Health Care Conference in New York City and will include an overview of the company’s ongoing development program for Tovaxin which is an individualized T-cell therapeutic vaccine that is being developed for the treatment of MS, and which recently yielded positive data from a Phase IIb clinical trial in which 150 patients participated in the multi-center, randomized, double blind, placebo controlled study for the treatment of the Relapsing-Remitting (RR) form of multiple sclerosis. Among other measurements, MRI scans showed statistically significant decreased lesions in those patients who had received Tovaxin.

Tovaxin, which requires only 5 subcutaneous injections per year, is an individualized T-cell therapeutic vaccine based upon attenuated patient-specific myelin-reactive T-cells against peptides of protein from myelin basic protein, myelin oligodendrocyte glycoprotein and proteolipid protein or combinations thereof. Tovaxin is manufactured in Opexa’s in-house cGMP facility.

Tovaxin’s dual mechanism of action combats the demyelination of the nerve fibers in the central nervous system, which is the underlying cause of MS. Clinical results have demonstrated that Tovaxin induces an immune response that depletes and regulates the circulating pathogenic myelin-reactive T-cells that are responsible for attacking the myelin sheath of nerve fibers. Additionally, Tovaxin also rebalances the systemic immune response by causing a shift from pathogenic inflammatory T-cells to anti-inflammatory T-cells.

Opexa Therapeutics is focused on the development and commercialization of patient-specific autologous (in which the donor and recipient are the same person) cellular therapies that are based upon proprietary T-cell and adult stem cell products for the treatment of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and diabetes. The Company holds the exclusive worldwide license for adult multipotent stem cells derived from mononuclear cells of peripheral blood, which allow large quantities of monocyte-derived stem cells to be produced efficiently for use in autologous therapy, thereby eliminating the risk of immune rejection. In addition to Tovaxin, the T-cell therapy for MS which is currently in Phase IIb clinical trials, Opexa is also in the preclinical development of another product for diabetes mellitus.

Pluristem Therapeutics, Inc., which specializes in the commercialization of adult stem cell therapy products for the treatment of degenerative, ischemic and autoimmune diseases, has demonstrated success in an animal model with a product that it has developed specifically for the treatment of multiple sclerosis (MS). Known as PLX-MS, for “PLacental eXpanded” cells, this product, which is derived entirely from adult stem cells, has proven to be effective in vivo. Specifically, mice that received PLX-MS did not develop clinical symptoms associated with MS when compared with control mice, for the entirety of the 35-day study. PLX cells are mesenchymal stromal cells that are derived from placental blood and then expanded under Pluristem’s proprietary technology.

According to Zami Aberman, president and CEO of Pluristem, “This trial’s remarkable results demonstrated our PLX-MS cells’ ability to prevent the appearance of multiple sclerosis symptoms and showed the potential for our PLX cells to treat global autoimmune diseases. As a cellular therapy, our PLX cells, which are derived from human placenta, a non-controversial, non-embryonic, adult stem cell source, and stored ready-to-use, could prove to be a readily available preventive therapeutic alternative for these disorders.”

The World Health Organization (WHO) estimates that approximately 2.5 million people throughout the world suffer from multiple sclerosis, which is an autoimmune, demyelinating disease of the central nervous system for which there has previously been no cure, and only limited therapies available prior to the advent of stem cell technology. At its current level, the global market for MS treatments has been estimated at approximately $5.4 billion per year, although this figure is expected to rise based upon epidemiological projections.

Pluristem Therapeutics Inc., a biotech company specializing in the commercialization of allogeneic adult stem cell therapy for degenerative, ischemic and autoimmune diseases, has been selected to present at the First Annual Israeli Presidential Conference entitled, “Facing Tomorrow”, to be held from May 13 -15 in Jerusalem. A total of 60 presenters were selected from among hundreds of candidates in the sciences, the arts, and business, all of whom represent inventions and innovative ideas that have been developed by Israeli individuals and which have the potential “to revolutionize the future”, in the words of Conference representatives. According to Pluristem’s President and CEO, Dr. Zami Aberman, “Pluristem is pleased to be invited to this high level international conference to present its business and products in development to world-renowned business leaders, technology thought leaders and entrepreneurs.”

A number of world leaders in the arts, the sciences, business and politics will attend the Conference, including U.S. President George W. Bush, Former British Prime Minister Tony Blair, Former President of the USSR Mikhail Gorbachev, Former U.S. Secretary of State Dr. Henry Kissinger, New York Times columnist Thomas L. Friedman, Chairman and CEO of News Corporation Rupert Murdoch, and Harvard Law Professor Dr. Alan Dershowitz.

Pluristem Therapeutics is currently developing a variety of novel adult stem cell products in their pipeline which are derived from the human placenta. As such, the products are strictly non-embryonic and non-controversial. The products consist of expanded placental mesenchymal stromal cells (MSCs) which are immune-privileged and which exhibit immunomodulatory properties. For the expansion of these MSCs, Pluristem uses a proprietary 3-dimensional bioreactor which is modeled after the natural microstructure of bone marrow matrix. Their main product in development, PLX-PAD, is targeted toward those millions of people who suffer from peripheral artery disease (PAD). Other products include PLX-1, which improves the engraftment of hematopoietic stem cells derived from umbilical cord blood, and PLX-Stroke which is for the treatment of ischemic stroke, and PLX-MS which is for the treatment of multiple sclerosis.

At the French National Institute for Health and Medical Research (INSERM), scientists have discovered the presence of neural stem cells in the human spinal cord. Although neural stem cells had previously been discovered in the brain and spinal cord of adult rodents several years ago, this marks the first discovery of neural stem cells in human brains and spinal cords. Such a discovery corroborates new supporting evidence that the human central nervous system (CNS) is in fact capable of regeneration – a radical idea which shatters the previously revered, though incorrect, dogma that the CNS is incapable of regeneration.

Using electron microscopy to detect neural precursor cell markers, the researchers at INSERM were able to identify and isolate adult neural stem cells from the human spinal cord. The stem cells were then cultured in vitro and found to differentiate into both neurons and glial cells. Research is now focused on the use of such endogenous neural stem cells in the treatment of neurodegenerative and demyelinating diseases such as multiple sclerosis and ALS (amyotrophic lateral sclerosis, or “Lou Gehrig’s disease”), as well as in the treatment of spinal cord injury (SCI). It is currently estimated that approximately a third of a million people throughout Europe, and a quarter of a million people in the U.S., suffer from SCI, with approximately 10,000 new cases occurring each year in each of these demographic regions. The majority of people who suffer SCIs are betweeen the ages of 25 and 30, and the resulting paralysis has often been regarded as permanent and irreversible.

Now, however, new hope is available as a reult of this important discovery that neural stem cells naturally reside within the CNS. According to Dr. Alain Privat, Research Director at INSERM, “This work constitutes a major step forward for all the pathologies affecting the motoneurons for which no treatment exists at the present time.”

The research was funded by the RESCUE (Research Endeavor for Spinal Cord in United Europe) Project, which in turn is funded by the European Commission FP6 Research Progrramme. RESCUE is a consortium of stem cell biologists and experts in spinal cord pathology from 9 European research centers, the mission of which is to advance novel stem cell therapies for spinal cord injury toward clinical trials. Known technically as translational medicine, such a process involves “translating” the results of experimental laboratory studies into clinical therapeutic paradigms. RESCUE researchers are dedicated to the implementation of such translational medical procedures specifically as applied to new therapeutic protocols for the treatment of SCI.

Pluristem Therapeutics Inc., which specializes in the commercialization of therapeutic products developed exclusively from adult mesenchymal stromal cells (MSCs) that are derived from the human placenta, has announced positive results with the use of one of its products in a pre-clinical animal study of multiple sclerosis. PLX-MS, which Pluristem is developing specifically for the treatment of multiple sclerosis, was tested in the EAE (experimental autoimmune encephalitis) animal model, which typically serves as the standard research paradigm for multiple sclerosis in humans. After EAE was induced in the animals, some of the animals were given PLX-MS while others served as controls. The animals that had received PLX-MS were found to show a statistically significant improvement in their EAE scores, which lasted throughout the entire 25-day duration of the study, when compared to the controls.

According to Dr. Zami Aberman, President and CEO of Pluristem, “We are very excited that our PLX cells were able to demonstrate beneficial results that are statistically significant in this standardized model for multiple sclerosis. These results, in addition to our previously announced PLX-Stroke results, demonstrate that PLX cells may be useful in the treatment of central nervous system disorders and may potentially help millions of people. Additionally, we believe this experiment demonstrates that we can potentially utilize our off-the-shelf, easy-to-obtain PLX cells and achieve results that are as good as or better than MSCs obtained from other more difficult-to-find sources.”

Multiple sclerosis, one of the demyelinating diseases, is a disorder of the central nervous system and is generally considered to be of autoimmune origin. According to recent estimates from the World Health Organization, over 2.5 million people around the world currently suffer from multiple sclerosis. Prior to adult stem cell research such as these studies conducted by Pluristem, multiple sclerosis has previously been considered incurable and irreversible. Now, however, adult stem cells and regenerative medicine offer a new type of therapeutic modality and, therefore, also new hope.

Currently in the state of Colorado, there are only three hospitals in which the systematic collection of umbilical cord blood is routinely performed after the delivery of babies. In all the rest of the hospitals throughout the state, as in most other states, this precious source of pluripotent stem cells is discarded as waste. Democratic House Representative Dianne Primavera sees this as “an opportunity to turn medical waste into a medical miracle.” Indeed, patients such as Sheila Gannon agree. Diagnosed with advanced leukemia over two years ago, Sheila received an adult stem cell transplant from donated umbilical cord blood. As she stated in her testimony before the State House Health and Human Services Committee, “We are extremely grateful for this technology and for the medical community that administers it. I often think about the moms who graciously donate their umbilical cord blood. There is no doubt that without this I would not be here today.”

Many others enthusiastic advocates joined Representative Primavera and Ms. Gannon in supporting what is known as House Bill 1372, which, if ratified, would create the Adult Stem Cell Cure Fund: a voluntary income tax checkoff that would appear on future state income tax forms, revenue from which would promote the proper collection and storage of umbilical cord blood throughout the state of Colorado.

As Representative Primavera described, she sees an analogy between the umbilical cord as a “lifeline for a baby” and a lifeline for someone with a disease such as cancer or multiple sclerosis. As Sheila Gannon added, “I cannot think of a better way to pay it forward than to give all women the opportunity to donate the baby’s umbilical cord blood.” Doctors testifying before the Committee stated that there are roughly 80,000 births each year in Colorado, less than 1% of which currently result in a cord blood donation. If House Bill 1372 is passed, it is hoped that the money raised by the income tax checkoff could be used both for promoting education on the topic as well as for the actual cryogenic storage of donated cord blood, possibly for as long as 20 years for each donation. According to Dr. Chris Carey, who runs the OB-Gyn department at the Denver Health Medical Center, “It is my belief that this bill offers a tremendous opportunity to improve the health of Coloradans for a relatively small expense.”

Thus far, the new measure has passed the Committee unanimously. Next, it advances to the House Appropriations Committee.