FDA Postpones First U.S. Clinical Trial of Embryonic Stem Cells

On April 10, 2008, the U.S. Food and Drug Administration (FDA) convened a panel of experts to examine the safety concerns associated with the use of embryonic stem cells in human clinical trials, in response to applications that were submitted by three companies, namely, Geron, Advanced Cell Technology, and Novocell. Consequently, the FDA issued a strong cautionary statement on the dangers of embryonic stem cells, although the three companies continued with their plans to commence clinical trials in the summer of 2008.

Yesterday, however, the company Geron received an oral notification from the FDA of a delay in the approval process that is required before clinical trials may begin. Based in Menlo Park, California, Geron had planned to begin human clinical trials for the treatment of acute spinal cord injuries in which they would test their proprietary compound made with human embryonic stem cells. Geron is now awaiting a formal letter of explanation from the federal regulators at the FDA.

According to Thomas B. Okarma, Geron’s CEO, “We are disappointed with this action given the interactions we had with the FDA over 3 years leading to the filing”, which consisted of an application that was 21,000 pages in length. According to Ren Benjamin, an analyst with the investment bank Rodman & Renshaw, Wall Street is not surprised by the FDA’s action which analysts regard merely as causing a temporary delay in, rather than a final end to, the clinical trial plans.

The panel of experts that was convened by the FDA in their April 10th meeting stressed the importance of stringent safety measures in embryonic stem cell trials. According to Dr. Steven Bauer, Acting Chief of the FDA’s Office of Cellular, Tissue and Gene Therapies, a branch of the Center for Biologics Evaluation and Research (CBER), the agency is likely to require “particularly strong” evidence to substantiate claims of embryonic stem cell safety and efficacy. Assuming that the clinical trials will be allowed to begin, the FDA may also require longer trials than those that are required for the approval of conventional drugs.

It is a well-established fact that embryonic stem cells cause the formation of a specific type of cancerous tumor known as a teratoma; indeed, such a feature of embryonic stem cells constitutes their defining trait. An embryonic stem cell is a cell which, by definition, forms a teratoma, and this remains the universal laboratory test by which embryonic stem cells are identified throughout the world. This test is the global scientific standard of measurement: if a cell forms a teratoma, then it is recognized as being an embryonic stem cell; if a cell does not form a teratoma, then it is recognized as being just an ordinary adult stem cell or some other type of cell. Adult stem cells, by stark contrast to embryonic stem cells, carry no such risk for the formation of teratomas. These facts are well known and well understood throughout the scientific community, and always have been, although they are not often reported to the general public by the media.

Ever since 1999, when an 18-year-old patient named Jesse Gelsinger died four days after receiving experimental gene therapy in a clinical trial, FDA regulators have been particularly sensitive to potential risks that may be associated with clinical trials, and justifiably so. Any further undesirable medical conditions that may result from clinical trials would not only constitute personal tragedies for the individuals involved, but such consequences would also constitute severe policy setbacks for the entire FDA approval process as a whole. Currently, with human embryonic stem cells, the dangers are already well documented and no successes to date have ever been reported or published. Thus far, human embryonic stem cells have never been used to treat any human disease or injury, precisely because human embryonic stem cells have proven to be so highly problematic in the laboratory. By dramatic contrast, however, adult stem cells are already being used in numerous clinics around the world to treat a wide variety of diseases and injuries, efficaciously and in most cases without any side effects.

Dispite the cautionary delay by the FDA, Geron, as well as Advanced Cell Technology and Novocell, are still planning to be able to begin human clinical trials with their proprietary embryonic stem cell compounds.

Researchers Report First Successful Creation of Heart Tissue From Adult Heart Stem Cells

Stem cells are known to reside in most types of tissue throughout the adult human body, but until recently it was believed that the heart is one region of the body which does not contain its own stem cells. Such a theory has now been proven to have been erroneous.

A number of recent studies have led to the identification of a small pool of stem cells that reside in the adult human heart, and now researchers in the Netherlands have successfully isolated these stem cells. Upon being cultured, the cells spontaneously developed into mature heart muscle that exhibits rhythmic contraction and is also responsive to electrical stimulation and adrenaline. According to Dr. Pieter Doevendans of the University Medical Centre in Utrecht, “We’ve got complete control of this process, and that’s unique. We’re able to make heart muscle cells in unprecedented quantities, and on top of it they’re all the same. This is good news in terms of treatment, as well as for scientific research and testing of potentially new drugs.”

Cardiac muscle is among the most specialized types of tissue in the body and is typically highly resistant to repair following damage such as that caused by a heart attack or acute injury. For this reason, conventional wisdom held that the heart must be devoid of stem cells, but now that it is known that the heart does in fact contain its own stem cells, further studies will investigate the precise role that such stem cells play in cardiac health and function. With the assistance of modern medical technology, such endogenous cardiac stem cells can ultimately be utilized in the treatment of heart disease and other cardiac problems.

Stem Cells From Menstrual Blood Offer New Hope in Organ Transplantation and in the Treatment of Numerous Diseases

Stromal cells are found in the endometrial lining of the uterus and are shed every month during menstruation. Stromal cells are also found in connective tissues throughout the body, and are known to differentiate into new cartilage, bone, fat, heart, skin and brain cells. Such cells are now the focus of intense research throughout the world, as the discovery of their presence in menstrual blood offers a new opportunity for easily and noninvasively collecting such prized cells. Known as MenSCs (menstrual blood stromal cells), these cells may be harvested from a potentially unlimited, inexpensive, and continuous source by methods that are free of ethical controversies.

According to Dr. Amit Patel, director of Cardiac Cell Therapy at the University of Pittsburgh’s McGowan Institute of Regenerative Medicine, “Uterine stromal cells have similar multipotent markers found in bone marrow stem cells and originate in part from bone marrow.” When the MenSCs were grown in the laboratory, the cells were found to divide very rapidly, even more rapidly than stromal cells that are harvested directly from bone marrow. Although MenSCs do not divide as fast as embryonic stem cells do, MenSCs also do not carry any of the risks that are associated with embryonic stem cells, such as the formation of a particular type of cancerous tumor known as a teratoma.

Cryo-Cell International was a partner in conducting the research. According to Julie Allickson, vice president of laboratory operations, research and development at Cryo-Cell, “The preliminary results are extremely encouraging and support the importance of further study of these cells in several different areas including heart disease, diabetes and neurodegenerative disease.” According to Dr. Dwaine Emerich, a section editor for Cell Transplantation, “These studies are a significant step forward in the development of transplantable stem cells for human diseases because they address major issues including routine and safe cell harvesting of renewable cells that maintain their differentiation capacity and can be scaled for widespread clinical use.”

It is believed that these rapidly dividing MenSCs may be of particular usefulness in those diseases that require organ transplantation. Instead of transplanting an organ that has been donated by someone, scientists will instead be able to grow a new organ, and the other new tissue that is needed, from MenSCs such as these.

These findings with MenSCs offer further substantiating evidence for the potency of endometrial regenerative cells (ERCs), the properties of which were first described by scientists of Medistem Laboratories, who published the first full elucidation of ERCs in the Journal of Translational Medicine in November of 2007 in an article entitled, “Endometrial Regnerative Cells: A Novel Stem Cell Population”. The Medistem scientists were then honored with an award by Biomed Central for the best research article of 2007 in medicine, which was presented at the Royal Society of Medicine in London in March of 2008.

Adult Stem Cell Company Selected for Prestigious Conference in Israel

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.

Neural Stem Cells Discovered in Adult Human Spinal Cord

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.

Phase III Clinical Trials Begin With Cord Blood Stem Cells in the Treatment of Metabolic Disorders in Pediatric Patients

Aldagen, Inc., a biopharmaceutical company specializing in the development of proprietary regenerative cell therapies, reports the commencement of Phase III clinical trials for their newest and most advanced adult stem cell product. Known as ALD-101, and believed to be able to accelerate neutrophil and platelet engraftment following cord blood transplantation, the product was developed from adult stem cells that were isolated from umbilical cord blood. 40 pediatric patients with inherited metabolic diseases who have been selected for the study will receive a cord blood transplant in combination with ALD-101. In previous Phase I and II clinical trials, 24 patients who received ALD-101 showed a statistically significant reduction in platelet engraftment time when compared to controls who had not received ALD-101.

A number of inherited metabolic diseases have already been shown to be treatable with adult stem cells derived from cord blood, including Adrenoleukodystrophy, Metachromatic Leukodystrophy, Krabbe’s Syndrome and Hurler Syndrome, all of which have few treatment options and are often fatal. Now, products such as these developed by Aldagen offer yet a further improvement in the efficacy of such therapies.

In addition to ALD-101, Aldagen also has several other adult stem cell products which include ALD-151, which is designed to improve cord blood transplants in the treatment of leukemias, ALD-301 which was developed for the treatment of critical limb ischemia, and ALD-201 which was developed for the treatment of ischemic heart failure.

Adult Stem Cells Show Positive Results in a Pre-Clinical Study of Multiple Sclerosis

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.

Cautionary Response Issued for Clinical Trials With Embryonic Stem Cells

Three biotech companies are currently preparing for their upcoming clinical trials that will test the therapeutic value of their proprietary embryonic stem cell products. In the midst of such preparation, the U.S. FDA (Food and Drug Administration) convened a panel of experts yesterday to examine the safety concerns associated with such proposed therapies, not the least of which is the risk of cancer.

It is a well-established fact that embryonic stem cells cause the formation of a specific type of cancerous tumor known as a teratoma; indeed, such a feature of embryonic stem cells constitutes their defining trait. An embryonic stem cell is a cell which, by definition, forms a teratoma, and this remains the universal laboratory test by which embryonic stem cells are identified throughout the world. This test is the global scientific standard of measurement: if a cell forms a teratoma, then it is recognized as being an embryonic stem cell; if a cell does not form a teratoma, then it is recognized as being just an ordinary adult stem cell or some other type of cell. Adult stem cells, by stark contrast to embryonic stem cells, carry no such risk for the formation of teratomas. These facts are well known and well understood throughout the scientific community, and always have been, although they are not often reported to the general public by the media.

The three companies under current scrutinization, namely, Geron, Advanced Cell Technology, and Novocell, are in the process of planning their imminent clinical trials to test embryonic stem cells in the treatment of, respectively, acute spinal cord injury, visual impairment, and diabetes. Following the announcement by the FDA, yesterday’s discussion among a panel of experts focused on the many unanswered questions that are associated with the as yet unproven safety and efficacy of embryonic stem cells.

Ever since 1999, when an 18-year-old patient named Jesse Gelsinger died four days after receiving experimental gene therapy in a clinical trial, FDA regulators have been particularly sensitive to potential risks that may be associated with clinical trials, and justifiably so. Any further undesirable medical conditions that may result from clinical trials would not only constitute personal tragedies for the individuals involved, but such consequences would also constitute severe policy setbacks for the entire FDA approval process as a whole. Currently, with human embryonic stem cells, the dangers are already well documented and no successes to date have ever been reported or published. Thus far, human embryonic stem cells have never been used to treat any human disease or injury, precisely because human embryonic stem cells have proven to be so highly problematic in the laboratory. By dramatic contrast, however, adult stem cells are already being used in numerous clinics around the world to treat a wide variety of diseases and injuries, efficaciously and in most cases without any side effects.

According to the authors of this review, “Scientists know that undifferentiated stem cells can form a benign mass known as a teratoma when injected into animals, and they fear that a safety incident in the first round of clinical trials could devastate the already-troubled field. The cell therapies under development use differentiated cells, but the possibility remains that some undifferentiated cells may be left in the mix.” While teratomas are technically classified as “benign”, in the sense that they do not metastasize, they do have a malignant counterpart known as a teratocarcinoma, which may also form from embryonic stem cells. It should also be noted that a person can die from either of these tumorous forms, including the so-called “benign” teratoma.

The committee convened by the FDA plans to release a formal guidance statement, formulated at yesterday’s meeting. Meanwhile, however, the 3 companies under consideration remain undaunted, with Geron in particular insisting that they will proceed with plans for clinical trials with embryonic stem cells that will commence in the summer of this year.

An Adult Stem Cell Bill Advances in the Colorado State Legislature

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.

Alzheimer’s Slowed by Stem Cells From Umbilical Cord Blood

More than 5 million people in the U.S. alone are currently afflicted with Alzheimer’s disease, and the global number is increasing dramatically each year. Now, researchers at the University of South Florida, in collaboration with Saneron CCEL Therapeutics, Inc., an affiliate of Cryo-Cell International, have demonstrated the ability of cord blood stem cells to slow the progression of this debilitating disease.

In this study, mice with symptoms mimicking those of Alzheimer’s were treated with a series of infusions containing stem cells derived from umbilical cord blood. The scientists then tested the mice for the two main markers of Alzheimer’s, and found that the myloid-beta proteins had been reduced by 62%, and cerebral amyloid angiopathy had been reduced by 86%. Currently, Alzheimer’s disease is considered to be irreversible since an effective conventional medical therapy does not exist. This study, however, demonstrates that Alzheimer’s disease can in fact be reversed with the potency of certain types of adult stem cells such as those derived from umbilical cord blood.

Although conservative groups often promote the use of adult stem cells over embryonic stem cells for ethical reasons, scientists are increasingly turning to adult stem cells over embryonic stem cells purely for scientific reasons. Increasingly, studies such as this indicate significant success with adult stem cells while embryonic stem cells still remain plagued with numerous unsolved scientific problems. According to Mercedes Walton, Chairman and CEO of Cryo-Cell International, an organization of cord blood banks which funded the study, “The scientific community has only skimmed the surface in uncovering the many potential therapeutic uses for cord blood stem cells, and this new research in Alzheimer’s disease may pave the way for discoveries around the use of these cells for a host of neurodegenerative and other chronic conditions.”

According to Dr. Jennifer Roback Morse, a senior fellow in economics at the Acton Institute for the Study of Religion and Liberty, “The use of umbilical cord blood is more humane than the use of embryos for two reasons. First, no human life has to be destroyed to produce the umbilical cord blood. Second, the use of umbilical cord blood will undoubtedly be less costly than the use of embryonic stem cells. The supply of umbilical cords is pretty much umlimited.”

Ever since 2004 when a South Korean woman who had been paralyzed for 20 years was able to walk again following cord blood stem cell therapy which repaired the damaged tissue in her spine, this particular source of adult stem cells has been a topic of of intense interest by numerous researchers and clinicians around the world. According to Cryo-Cell, cord blood offers one of the most viable sources of stem cells, as cord blood has already been used in over 7,000 transplantations since 1988, and stem cells derived from cord blood have been clinically administered to human patients for the treatment of more than 70 life-threatening illnesses, which include cardiac injury, neurological injury, type I diabetes, type II diabetes, leukemia, multiple sclerosis, and numerous other types of diseases and injuries.

Next, Alzheimer’s disease may also be added to the list.