Multiple Sclerosis Successfully Treated Yet Again With Adult Stem Cells

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.

The Stem Cell Revolution

The February 9th, 2009 issue of Time Magazine features a cover story entitled, “How the Coming Revolution in Stem Cells Could Save Your Life.” Plastered across the magazine’s front cover is a photograph of a colorful pink and blue blob which is identified as an “induced pluripotent stem cell from an ALS (amyotrophic lateral sclerosis) patient.”

Not surprisingly, this is not the first time that the topic of stem cells has been chosen for the cover of Time Magazine. Among their numerous articles on the subject and its related personalities over the years, Time Magazine also featured a cover story about stem cells in the August 7th, 2006 issue, entitled, “The Truth About Stem Cells: The Hope, The Hype, and What it Means For You”. At that time, plastered across the front cover of the magazine was a microscopic enlargement of a pink and green blob which was identified as an “adult bone marrow stem cell”. The 2006 cover story was ten pages long, 9 pages of which contained text; by comparison, this year’s cover story is only 6 pages long, a mere 5 pages of which contain text. Given the rapid pace of advancements that have transpired in the stem cell field over the past 3 years, one might logically expect a recent article on the topic to be at least as long as, if not even longer than, an article that was written 3 years ago; and perhaps the 2009 article might have been longer than it is, had the author thought to include the topic of adult stem cells. But, for whatever reason, and unlike the 2006 article, the 2009 article is instead devoted exclusively to the topic of everything else but adult stem cells.

In the 2006 article, the reader’s eye was immediately drawn to a two-page illustration of stem cells stretching across pages 42 and 43 of the issue, which is strikingly similar to the two-page illustration that also stretches across pages 42 and 43 of the 2009 issue. As in the 2006 issue, as one might expect, the co-director of Harvard’s Stem Cell Institute, Dr. Douglas Melton, is also extensively interviewed in the 2009 issue. Unlike the 2006 issue, however, the 2009 issue is devoted exclusively to descriptions of research with embryonic stem cells and iPS (induced pluripotent stem) cells, with practically no mention whatsoever of adult stem cells nor of the extraordinary progress that has already been achieved with adult stem cell therapies. In fact, rather than being a scientifically objective presentation of the pros and cons of various types of stem cells, the 2009 article appears to be more along the lines of either a personal biographical tribute to Douglas Melton, or a form of retribution directed against “the dark days of the Bush Administration’s stem-cell restrictions”, or both. But balanced and unbiased, it is not.

Indeed, the 2009 Time Magazine cover story points out, in reference to Dr. Melton’s work, that “Melton’s motivation was, again, both professional and intensely personal,” since this distinguished scientist has two children who suffer from type 1 diabetes: a son who was diagnosed with the disease 17 years ago at the age of 6 months, and a daughter who was also diagnosed with type 1 diabetes 8 years ago at the age of 14. Certainly, no reader would question the relevance nor the importance of personal experiences such as these, which were highly influential in changing the entire direction of Dr. Melton’s career. One does, however, question how it is possible that, in any article which claims to inform readers about a “coming revolution in stem cells” which might “save your life”, the author of the article could systematically avoid all mention of adult stem cell therapies which already exist and which have already been saving lives in clinics around the world. Instead, in an article which purports to inform readers about medical therapies which are so urgently and desperately needed by so many people, not only by Dr. Melton’s children, the author of this article chooses only to feature embryonic stem cells and iPS (induced pluripotent stem) cells, which do not exist at all as therapies. Indeed, the safety and efficacy of embryonic and iPS cells are so questionable that it might be another decade or longer before such cells can be used as clinical therapies, assuming that they can ever be safely and effectively used as clinical therapies at all. And yet, in this article, embryonic stem cells and iPS cells are inaccurately presented as the only possible source of future stem cell therapies for people who are suffering from disease and injury. Perhaps adult stem cells were entirely and mysteriously excluded from this article because adult stem cells do not represent a “coming revolution” but instead represent a current revolution that has already arrived and is already fully upon us and is already taking place at this very moment, in the here-and-now, on a global basis, if anyone would care to notice. By sharp contrast to adult stem cells, however, the therapeutic viability of embryonic stem cells and even of iPS cells is still entirely hypothetical and no one can predict with any certainty when, if ever, embryonic or iPS cells might be available as clinical therapies, but even the most determined of embryonic stem cell experts do not expect embryonic stem cell nor iPS cell therapies to be available in less than a decade.

If there are any dangers that are associated with adult stem cells, or if there had ever been any problems that were ever found with the numerous FDA-approved clinical trials that have already been conducted with adult stem cells, then this would have been the place to highlight and feature such dangers and problems; but instead, the entire topic of adult stem cells is categorically ignored altogether throughout this 2009 Time Magazine cover story. Nowhere to be found at all, adult stem cell therapies are conspicuous by their absence from the whole article. Of course, the numerous clinical applications of adult stem cells have only yielded dramatic successes, not failures, but apparently the purpose of this article was not to inform the public of successful medical breakthroughs that have already occurred. Instead, the purpose of this article seems to have been to inflate public hopes and expectations for future medical breakthroughs that might not ever occur. Oddly enough, however, the author of this 2009 Time Magazine article does acknowledge some, though not all, of the dangers associated with embronic and other types of pluripotent stem cells, as the author clearly states, “Even iPS cells have yet to prove that they are a safe and suitable substitute for the diseased cells they might eventually replace in a patient. Ensuring their safety would require doing away with dangerous genes that can also cause cancer, as well as the retroviral carriers that Yamanaka [the discoverer of iPS cells] originally used.” But nowhere in this article are teratomas ever mentioned, despite the fact that the ability of an embryonic stem cell, and an iPS cell, to form this particularly hideous and dangerous type of tumor is, by definition, one of the requirements by which embryonic and iPS and other types of pluripotent stem cells are identified in laboratories throughout the world. Interestingly, the author makes reference to Geron’s highly publicized upcoming clinical trial with human embryonic stem cells – the first of its kind, and the first ever to attain approval from the U.S. FDA – without actually mentioning the Geron Corporation by name, and also without ever mentioning any of the problems that are inherent in this clinical trial. (Please see the related news article on this website entitled “Geron’s Efforts in Europe are Thwarted”, dated February 13, 2009). Geron’s clinical trial has not even begun patient enrollment yet, and data from the Phase I trial will not even be available until 2011 at the earliest, yet nevertheless this clinical trial was deemed worthy of mention in the article, even though, for whatever reason, the name of the Geron Corporation itself was not; however, nowhere in the article is there any mention whatsoever of any of the adult stem cell companies that have already conducted FDA-approved clinical trials with adult stem cells, such as, most obviously, Osiris Therapeutics, which is already legendary within the scientific community for its pioneering work and repeated, consistent success with its adult stem cell therapies in a number of FDA-approved clinical trials that have already advanced to Phase III. Of course, the fact that Osiris Therapeutics is never mentioned even once in this article would, presumably, have nothing to do with the fact that Osiris Therapeutics is strictly an adult stem cell company, the exclusive focus of which is the development of clinical therapies from adult stem cells, not from embryonic stem cells. Certainly, members of the media would never be biased against adult stem cell companies; instead, we can only give members of the media the benefit of the doubt by magnanimously concluding that they simply don’t understand the scientific and medical differences between these various types of stem cells and stem cell companies, because if they did understand the differences, they would be blowing trumpets from the rooftops of their buildings in excitement over the revolutionary life-saving successes that have already been achieved with adult stem cells.

Some statements within the 2009 Time Magazine article are fundamentally inexplicable, and leave anyone with a true scientific understanding of stem cells scratching his or her head, such as the statement that, “…embryonic stem cells remain the gold standard for any treatments that find their way into the clinic…”, which is a puzzling cliam, to say the least, especially in light of the fact that embryonic stem cells have never advanced to any type of treatment that has ever found its way into the clinic at all. The only type of “gold standard” with which embryonic stem cells are associated is their ability to form the specific type of tumor known as a teratoma, which literally is the “gold standard” by which laboratories around the world identify embryonic and iPS and all other types of pluripotent cells, since the ability to form a teratoma is part of the official scientific definition of pluripotency. Don’t expect to find any mention of teratomas, however, in this article, nor a fairly representative reporting of scientific discoveries and advancements in the stem cell field, since such facts and perspectives are not to be found here. Regarding “treatments that find their way into the clinic”, only adult stem cells, not embryonic stem cells, have ever advanced to the level of actual therapies that have ever found their way into the clinic, yet this fact is never mentioned, not even once, in this entire 2009 Time Magazine article; to the contrary, there seems to be a concerted effort made throughout this article to create the exact opposite, and entirely erroneous, impression.

Of course, the 2006 Time Magazine cover story on stem cells was not without its inaccuracies either. In that issue, in a small side-paragraph entitled “umbilical-cord cells”, under the subheading “Drawbacks”, the author wrote, “An umbilical cord is not very long and doesn’t hold enough cells to treat an adult.” If sentences such as this don’t leave legitimate stem cell scientists cross-eyed and scratching their heads, nothing will, and the most common reaction among scientists that this type of statement most frequently evokes is a simple, “huh?” Apparently, the author of the 2006 Time Magazine cover story had never heard of cell isolation or expansion – even without which, umbilical cord blood is still one of the most plentiful and overly-abundant sources of adult stem cells in the world, being freely and easily accessible everywhere throughout the world, on a daily basis, to such an extent that at any given moment we actually have much more than we could ever possibly use, even if we wanted to treat the entire population of the planet. Even the adult stem cells known as ERCs (endometrial regenerative cells), which are collected in even smaller volumes than umbilical cord blood, are expandable to quantities that outnumber the human population of the planet. Furthermore, given the numerous chemical, molecular and immunological properties of adult stem cells derived from umbilical cord blood, all of which are highly advantageous properties, it is laughable to cite the physical length of an umbilical cord as a “drawback”. But of course, journalists are not usually scientists, and therefore should not be expected to think and reason as scientists do, even though journalists have taken upon themselves the very serious responsibility of reporting scientific news, presumably in an accurate and truthful manner. It could hardly be considered complex science to make the simple observation that children are born every day throughout the entire world, and therefore umbilical cord blood is abundantly available every day throughout the entire world; yet somehow, in an article that was published in 2006 in one of the leading and most trusted magazines in the world, even this simple and obvious fact was lost and obscured by an irrelevant and scientifically false comment.

If anyone really cared about helping the people who suffer from disease and injury and who could benefit from stem cell therapy, and who are in fact in desperate and urgent need of such therapy, would it not seem reasonable at least to mention the FDA-approved clinical trials and actual clinical successes that have already been achieved with adult stem cells? Especially among scientists and journalists, how is it conscienable to completely, categorically, systematically ignore even the mere mention of adult stem cell therapies, when there are numerous people for whom such adult stem cell therapies could literally make the difference between life and death?

At least the 2006 article did mention that adult stem cells “exist in many major tissues, including the blood, skin and brain. They can be coaxed to produce more cells of a specific lineage and do not have to be extracted from embryos.” Strangely, the 2009 article fails to mention even this basic fact. The 2006 article did, despite its other flaws, at least point out that umbilical cords are “useful” because, according to the author, “Although they are primarily made up of blood stem cells, they also contain stem cells that can turn into bone, cartilage, heart muscle and brain and liver tissue. Like adult stem cells, they are harvested without the need for embryos.” By comparison, the 2009 article makes no mention whatsoever of umbilical cord blood at all, nor, in fact, is there any mention whatsoever of adult stem cell therapies, period. There is barely any mention of the fact that there is such a thing as adult stem cells and that they exist at all. In a semantically ambiguous phrasing of words, there is a reference in the 2009 article to stem cells that “can be created from adult cells”, which is stated in a partial sentence that hangs in mid-air next to an illustration of an “egg cell” in which somatic cell nuclear transfer, “genetic transfer” with retroviruses and four genes, and “safer transfer” with “chemicals or safer viruses”, are symbolically depicted. Of course, stem cells that are “created from adult cells” are not the same as “adult stem cells”, since the former (referring to iPS cells and to those other types of cells that are created by somatic cell nuclear transfer, “genetic transfer” and “safer transfer”, whatever exactly that will turn out to be) still pose a number of risks including tumor formation, whereas the latter (adult stem cells) do not pose any such risks, which is precisely why the former do not exist as clinical therapies whereas the latter (adult stem cells) do; but exactly how the non-scientific reader would ever be able to deduce such facts from this article is anyone’s guess. If nothing else, at least the adult stem cells known as mesenchymal stem cells, which are derivable from bone marrow as well as umbilical cord blood, could have been mentioned somewhere in this article, since these cells have already enjoyed a very well documented clinical history for decades. But alas, apparently even mesenchymal stem cells were forbidden from enjoying the right to “equal opportunity” in this article. The mere title of this cover story, “How the Coming Revolution in Stem Cells Could Save Your Life”, might logically imply some mention of the types of stem cells that have already saved lives, and which have already achieved a revolution in medical science; and those types of stem cells are adult, not embryonic, stem cells. Instead, perhaps the cover of this particular issue of Time Magazine could have been more accurately entitled, “How the Dangerous and Problematic Embryonic and iPS Cells Might Never Be Developed into Therapies That Could Save Your Life.”

If nothing else, the most recent, 2009 Time Magazine cover story does manage to offer resounding proof of an explanation for one long-standing mystery, which is, namely, why the general public is usually so confused about stem cells. Without objective and balanced scientific reporting, especially from the most established and respected names in the media, of course the average non-scientific lay person cannot be expected to understand even the most fundamental of scientific facts and principles behind any particular issue. In a few more years, perhaps some time around 2012 or so, maybe Time Magazine might publish yet another cover story about stem cells, by which time perhaps the publishing powers-that-be might not completely and deliberately ignore the increasing number of successes that are being achieved every day with adult stem cells, nor the increasing number of dangers and risks that are inextricably linked to embryonic stem cells and to iPS cells. Perhaps it will take a few more years before it is once again “politically correct” even to mention the topic of adult stem cell therapies, and thereby to publish a scientifically objective article about a critically important scientific field. The very same people who accuse the previous Administration of using politics and ideology instead of science to dictate policy, are in fact now guilty themselves of the very same thing, as they attempt to impose their own personal biases and prejudices upon others through the exact same fatally flawed approach. Hopefully, at some time in the future, perhaps both sides of the great political and ethical divide might be able to agree upon the same scientific facts; but how many people will die in the next few years, as they patiently wait for the media to get around to reporting accurately and truthfully about medical therapies with adult stem cells that already exist and are already available?

One thing is certain, though, as Dr. David Scadden, co-director of the Harvard Stem Cell Institute, is quoted as saying in the 2009 Time Magazine article: “It’s a wonderful time [for the stem-cell field]. Keep your seat belt on, because this ride is going to be wild.” At the very least, no one can argue with that claim.

Multiple Sclerosis Patients Improve After Adult Stem Cell Therapy

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.

Neuralstem Receives Patent for Neural Stem Cell Immortalization Technology

Representatives of Neuralstem have announced that the company received official “Notice of Allowance” from the U.S. Patent and Trade Office, for its technology that will immortalize stable neural stem cell lines.

The newly patented process utilizes cMyc-ER, which is a recombinant fusion of two proteins that are normally present in cells, namely, the estrogen receptor (ER) which is a human protein activated by estrogen, and c-Myc, which is a protein that regulates the human cell cycle.

According to Neuralstem president and CEO Richard Garr, “We are pleased to have received the Notice of Allowance on this important technology. The technology behind this patent allows us to grow practically unlimited quantities of neural stem cells from all regions of the brain without regard to the natural mitotic limits of cells from a particular region. Equally important, this technology is a next-generation immortalization process that avoids the harmful effects of traditional immortalization methods, which have invariably resulted in uncontrolled growth. Our technology provides the necessary assurance that the cell lines are fully controlled and remain consistent, trial over trial and year after year. This consistency is ultimately key to the commercialization of any cell products and greatly enhances our ability to deliver cell therapies for very prevalent diseases, such as stroke and traumatic brain injury. It will also enable, for the first time, systematic drug screening against many different kinds of normal human brain cells for new central nervous system drugs, and stem cell-mediated protein delivery for neurologic diseases.”

Neuralstem’s patented technology allows, for the first time, the production of neural stem cells from the human brain and spinal cord in commercial quantities, and for the controlled differentiation of these cells into human neurons and glial cells.

Researchers at Neuralstem are focused on major pathologies of the central nervous system including Huntington’s disease, ischemic spastic paraplegia, traumatic spinal cord injury, and amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease. In December of 2008, Neuralstem filed an IND (investigational new drug) application with the FDA for ALS and has also entered into a collaborative agreement with Albert Ludwigs University in Freiburg, Germany to develop clinical trials for Huntington’s disease.

FDA Approves First Human Embryonic Stem Cell Trial

In a controversial landmark decision, the U.S. Food and Drug Administration (FDA) has granted approval to the California-based biotech company Geron to commence the first human clinical trials ever to be conducted with embryonic stem cells. The trials, which are scheduled to begin in the summer of 2009 at 7 participating medical centers, will consist of administering embryonic stem cells in 8 to 10 paraplegic parients at the site of injury as soon as possible after an injury but no later than 2 weeks following an injury, before scar tissue has had time to develop. The objective of Phase I of the trials, which will be limited to patients with injuries in the middle of the spine, will be to evaluate safety. Evaluations of efficacy, in the form of patient improvement, will come later. Participating patients will also receive immunosuppressive drugs for the first couple of months in order to help minimize the risk of immune rejection. Follow-up will last for at least one year.

According to Dr. Thomas B. Okarma, Geron’s president and CEO, “This approach is one that reaches beyond pills and scalpels to achieve a new level of healing.” Nevertheless, the procedure comes with a disclaimer, since the treatment is neither expected to be a total nor an immediate cure, nor are patients expected to experience a significant restoration of function. As Dr. Okarma explains, “Any return of bladder or bowel function, a return of sensation, or a return of lower extremity locomotion would be a very exciting finding.”

Similarly, Peter Kiernan, chairman of the Christopher And Dana Reeve Foundation, is hopeful but cautious not to inflate expectations unrealistically. As he explained, “Of the millions of people dealing with paralysis in our nation, they are all delighted with subtle increases in function. We eat, drink, sleep getting people out of wheelchairs, but the reality of the world we are in is if people get bowel function, some sexual function, some ability for movement, that’s a wonderful outcome.”

The embryonic stem cells that will be used in Geron’s clinical trials were obtained from one of the already existing embryonic stem cell lines that former President Bush had approved for research, and is unrelated to President Obama’s promises of policy changes, which have yet to occur.

However, a number of million-dollar questions still remain unanswered, especially those related to whether or not immunosuppressive drugs will be enough to prevent an immune rejection of the stem cells, and whether or not these embryonic stem cells will cause teratomas in the patients. Time will tell.

The ability of embryonic stem cells to form the specific type of tumor known as a teratoma is the universal laboratory test by which embryonic stem cells are identified, since the ability to form a teratoma is, by definition, the measure of pluripotency. In stem cell laboratories throughout the world, if a cell is able to form a teratoma, then it is recognized as being an embryonic stem cell or some other type of pluripotent stem cell, but if it is not able to form a teratoma then it is recognized as being some other type of cell which is not embryonic and which lacks pluripotency. It is precisely for inherent medical risks such as teratomas that embryonic stem cells had not received previous FDA authorization to be used in clinical trials in the U.S., prior to Geron. Since adult stem cells are not pluripotent but instead are multipotent, they do not pose the risk of teratoma formation which is why adult stem cells are already being used in clinics around the world to treat patients with a wide variety of diseases and injuries. By sharp contrast, scientists agree that any hope of a safe and effective clinical therapy being developed from embryonic stem cells is still at least another decade away, if not further.

The cost of the therapy also remains an unknown factor, as well as the extent to which such a medical expense might be covered by insurance. No doubt all questions will be answered in time, however.

Attaining FDA approval to begin the testing of embryonic stem cells required what has been described by many in the field as a herculean effort, which cost Geron more than $150 million dollars in preliminary research that was conducted over a span of 13 years. Now, many more years of expensive clinical trials will still be required before the FDA can consider approving Geron’s embryonic stem cells for availability on the U.S. market.

Geron Corp. was heavily involved in the funding of Dr. James Thomson’s laboratory at the University of Wisconsin at Madison in the 1990s, when Dr. Thomson became the first person to isolate an embryonic stem cell, first from a primate in 1995 and later from a human in 1998. Current plans at Geron are also in progress for the development of embryonic stem cells in the treatment of heart failure and in the growth of insulin-producing beta islet cells for the treatment of Type 1 diabetes.

Opexa Briefs Shareholders on Corporate Update

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.

Mesoblast Announces Approval of First Osteoarthritis Clinical Trial Utilizing Adult Stem Cells

The Australian company Mesoblast has received institutional ethics approval to begin clinical trials with its adult stem cell product, RepliCart, in the treatment of osteoarthritis of the knee.

Headquartered in Melbourne, Mesoblast is now approved to begin randomized, placebo-controlled, double-blind Phase II clinical trials for its off-the-shelf allogeneic stem cell product, “RepliCart”, in the treatment of osteoarthritis of the knee in patients who have undergone reconstruction of a ruptured anterior cruciate ligament (ACL) within 6 months of a traumatic knee injury. The clinical trials will enroll 24 patients between the ages of 18 and 40 who will either be administered RepliCart in combination with hyaluronan, or just hyaluronan alone. The primary endpoint of the study will measure safety at 12 months, and a secondary endpoint will measure the prevention of cartilage loss and of knee osteoarthritis over time. Preclinical trials were successful in demonstrating the ability of a single injection of the allogeneic stem cells contained in RepliCart to regenerate joint cartilage and prevent osteoarthritis in animal models.

According to orthopedic surgeon Andrew Shimmin, from the Melbourne Orthopedic Research Foundation and the lead investigator of the clinical trials, “ACL injury is very common in our young active sporting population and unfortunately the injury is associated with the early development of arthritis despite modern reconstructive procedures. Little has changed in the prevention and treatment of arthritis over the past 50 years, so the application of Mesoblast’s stem cell technology for reducing the progression of this degenerative process in the knee offers a new and exciting direction for the management of arthritis.”

As Mesoblast’s executive director, Dr. Silviu Itescu, explains, “Commencing this clinical trial in post-traumatic knee osteoarthritis is an important step towards accessing the huge commercial opportunity that exists today for Mesoblast in the osteoarthritis market.”

It has been estimated that more than 15 million people in the U.S. alone suffer from osteoarthritis, which is a degenerative disease characterized by loss of cartilage. Osteoarthritis constitutes the most common form of musculoskeletal disorders among the elderly, in whom it is the primary cause of disability and joint pain. In the past, joint replacement has been the only option for such patients, but now stem cell therapy offers the first type of treatment that may actually reverse damage and regenerate joint tissue.

For people who suffer a ruptured anterior cruciate ligament (ACL) of the knee, which is more commonly and simply known as ruptured knee, 70% of the patients will develop osteoarthritis 15 to 20 years earlier than the general population, regardless of whether or not they have undergone reconstructive knee surgery. In the U.S. alone there are approximately 300,000 new cases per year of osteoarthritis having developed after an acute traumatic incident, not only in the elderly but in people of varying ages.

Mesoblast Limited is focused on the treatment of orthopedic conditions via the rapid commercialization of proprietary adult stem cell products that are designed for the regeneration and repair of bone and cartilage. As such, Mesoblast has the worldwide exclusive rights for a series of patented technologies that were developed over a period of more than 10 years and which are built upon the utilization of adult mesenchymal precursor cells (MPCs). As described on their website, Mesoblast has acquired 39% equity in Angioblast Systems Inc., which is a private New York-based biotechnology company that is developing the platform MPC technology for the treatment of cardiac, vascular and eye diseases including the repair and regeneration of blood vessels and heart muscle. Together, Mesoblast and Angioblast are jointly funding and advancing the core technologies behind such therapies.

Cardiac Dysfunction Secondary to Diabetes is Treated with Adult Stem Cells

Researchers in Cairo have successfully demonstrated the ability of adult stem cells derived from bone marrow to treat cardiac dysfunction that is secondary to diabetes in a rat model.

Previously, adult mesenchymal stem cells (MSCs) derived from bone marrow have already been used for the treatment of a number of non-hematopoietic diseases, such as for various cardiac, liver and kidney conditions, among other ailments. Now, however, Dr. Abdel Aziz and his colleagues in the Department of Medical Biochemistry in the Faculty of Medicine at Cairo University have published the results of a study investigating the effects of MSCs on cardiovascular complications resulting from Type 1 diabetes in rats. The study is unique because it is the first of its kind to offer an adult stem cell treatment for chronic cardiac dysfunction, which is significantly different from cardiac dysfunction that is caused by an acute event such as a heart attack. Following an acute cardiac event or injury, the body normally releases therapeutic chemokines which stimulate the homing action of endogenous stem cells and which also play a role in enhancing the efficacy of exogenously administered stem cells. In the current study, such naturally occurring chemokines and their corresponding healing action were not part of the therapy.

In the study, MSCs were derived from the bone marrow of male albino rats and infused into female diabetic rats. Serum insulin, glucose and fibrinogen were estimated and physiological cardiovascular functions such as heart rate and systolic blood pressure were assessed by a Langendorff apparatus. At the conclusion of the study, not only had cardiac and diabetic conditions both improved, but Y-chromosome positive cells were found in the both the cardiac and pancreatic tissue of the female recipient rats, demonstrating that the observable therapeutic effects were in fact the result of the male stem cells.

As Dr. Aziz and his colleagues concluded, “Rat bone marrow harbors cells that have the capacity to differentiate into functional insulin-producing cells capable of controlling blood glucose levels in diabetic rats. This may provide a source of cell-based therapy for diabetes mellitus. Furthermore, MSC transplantation can improve cardiac function in diabetes mellitus.”

Pluristem to Begin Adult Stem Cell Clinical Trials for Critical Limb Ischemia

The stem cell company Pluristem Therapeutics has filed an IND (investigational new drug) application with the U.S. FDA and its European counterpart to begin Phase I clinical trials for the treatment of critical limb ischemia with the proprietary adult stem cell product PLX-PAD, an allogeneic placental-derived stromal cell product.

The trials, which are to be conducted at clinical sites in the U.S. and Europe, will enroll patients who are suffering from “late stage” limb ischemia that has been unresponsive to conventional medical and surgical interventions, and for whom amputation is the only other remaining option.

As the president and CEO of Pluristem, Zami Aberman, explains, “We are pleased to be filing this IND application in the U.S.. Following approval by the FDA, we will begin administering PLX-PAD to patients afflicted with critical limb ischemia with the goal of proving this product safe. The IND application filed with the FDA and the IMPD (investigational medicinal product dossier) application filed in Europe are two important steps in Pluristem’s global strategy to become a dominant player in the cellular therapeutic business arena.”

According to Edwin M. Horwitz, M.D., Ph.D., Director of Cell Therapy in the Division of Oncology and Blood and Marrow Transplantation at the Children’s Hospital of Philadelphia, and chairman of Pluristem’s Scientific Advisory Board, “This is an exciting time for Pluristem. Success in this endeavor will signify the first time an adult stem cell, derived from the placenta and grown using the company’s PluriX 3D technology, has been administered to humans safely. This will represent a major advance in cell therapy and position Pluristem as an international leader in the field.”

As Dr. Brian Annex, Chief of the Division of Cardiovascular Medicine in the Department of Medicine at the University of Virginia School of Medicine, and a member of Pluristem’s Scientific Advisory Board, adds, “If Pluristem’s clinical trial is successful, this will be a major advance in the field of cellular therapeutics with the use of an allogeneic off-the-shelf product that needs no matching for peripheral vascular disease and then, potentially, other diseases.”

It has been estimated that between 8 and 12 million people in the U.S. alone suffer from critical limb ischemia (CLI), an advanced stage of peripheral artery disease (PAD). Industry analysts have estimated the market potential for the treatment of CLI to be over $1 billion, although conventional medical treatments of this life-threatening condition are often unsuccessful, thereby leaving a therapeutic void which cell-based therapies are uniquely qualified to fill.

Pluristem Therapeutics is focused on the development and commercialization of off-the-shelf allogeneic cell-based therapies for the treatment of chronic degenerative ischemic and autoimmune disorders. As described on their website, Pluristem specializes in adherent stromal cells (ASCs) that are derived from the placenta and which “are multipotent adult stem cells that have strong anti-inflammatory properties and can regenerate and repair damaged tissue.” ASCs have already been shown to differentiate into nerve, bone, muscle, fat, tendon, ligament, cartilage and bone marrow stroma. Additionally, since they have low immunogenicity, ASCs do not require HLA (human leukocyte antigen) matching and are not at risk of being rejected by the patient’s immune system.

After the ASCs are harvested from placental tissue, the cells are then expanded three-dimensionally into PLX (PLacental eXpanded) cells via the company’s proprietary PluriX 3D bioreactor, in which the cells are able to excrete their own cytokines and other immune modulators without the need for supplemental growth factors nor other exogenous materials. Like ASCs, PLX cells exhibit immunomodulatory properties and are “immune privileged” and as such do not pose any threat of immunological rejection.

As adult stem cells which are derived from the human placenta, which is an extremely rich non-embryonic source of stem cells, ASCs are also ethically non-controversial in addition to being highly potent adult stem cells.

Multiple sclerosis patient will take treatments at Cellmedicine

Mary Posta suffers from an advanced form of multiple
sclerosis termed