In the latest chapter of the ongoing saga over the first clinical trial ever to be conducted with human embryonic stem cells (hESCs), a new delay has presented itself.

Specifically, representatives of the Geron Corporation have announced today that U.S. federal regulators have placed a halt on the clinical trial that Geron was scheduled to conduct, before even one patient could be enrolled in the study.

Although a number of people among the non-scientific communities have expressed surprise over what they consider to be an unexpected announcement, there are many among the scientific community who find such a delay to be completely unsurprising and even predictable.

Frought with doubts and problems from the very start, the clinical trial was intended to use hESCs in the treatment of spinal cord injury. Because it would have been the first such study ever to be conducted with hESCs, the proposed clinical trial has repeatedly been the subject of widespread speculation and controversy. Now, this new ruling by the FDA, which brings all the momentum of the entire project to a grinding halt, has merely incited a new round of speculation and controversy.

The U.S. federal regulators decided to impose a halt on the clinical trial as a direct result of new data that Geron disclosed to the FDA, regarding dose escalation in preclinical animal studies. In January of this year, the FDA lifted an additional halt that it had previously imposed on Geron in May of 2008. This time, the new halt is based on safety concerns triggered by the new higher-dose data.

According to Joseph Pantginis, an analyst with the Merriman Curhan Ford Group in New York, "They are at the forefront, which a lot of times is a bit of a curse. They have to hit all the hurdles and be the first one to learn about how these cells behave."

In an official statement issued by representatives of Geron, the company "will work closely with the FDA to facilitate their review of the new data and to release the clinical hold."

Anna Krassowska, a spokesperson for Geron, stated to the press that the company had no further comment.

The news release posted on Geron’s website was brief, at only two paragraphs in length, not counting the customary "forward-looking statements" and "safe harbor" disclaimers. As stated on the comapny’s website, "GRNOPC1, a cell therapy for neurologically complete, subacute spinal cord injury, has been placed on clinical hold by the FDA pending the agency’s review of new nonclinical animal study data submitted by the company. A clinical hold is an order that the FDA issues to a sponsor to delay a proposed trial or to suspend an ongoing trial. … No patients have yet been treated in this study."

As the New York Times article concludes, "While thousands of patients around the world have been treated with adult stem cells and have shown mixed results, no humans have been given cells derived from embryos in an approved trial."

Indeed, it would seem as though, once again, embryonic stem cells remain confined to the experimental, laboratory stage, unable to progress to clinical trials. Meanwhile, by comparison, numerous types of adult stem cells have already advanced to Phase III clinical trials and beyond, and in fact have already been in use as viable therapies in clinics around the world for years.

Dr. Feng Lin, director of research at Bio-Matrix Scientific Group and its subsidiary Entest Biomedical, believes that traumatic brain injury (TBI) could possibly be cured with autologous adult stem cells derived from adipose (fat) tissue.

According to Dr. Lin, "Currently there is no effective therapeutic approach to reverse the initial brain damage caused by trauma. Brain cells or neurons have limited ability for self-repair and spontaneous axonal regeneration. Extensive studies have been focusing on novel therapeutic strategies for traumatic brain injury. In my opinion, adipose-derived stem cells could possess the capacity for self-renewal and differentiation into diverse cell types such as neural cells. We could be looking at an exciting and potential cure for traumatic brain injury patients."

Both Bio-Matrix and Entest Biomedical are currently studying the ability of adipose-derived stem cells (ASCs) to regenerate damaged neurological tissue and to repair the inflammation and brain ischemia that result from TBI. Together, Bio-Matrix and Entest have recently submitted a research proposal to the U.S. Army Medical Research and Material Command (USAMRMC) for funding to investigate an ASC therapy for TBI, which is a common problem among U.S. soldiers returning from Afghanistan and Iraq, where roadside explosives are a frequent cause of TBI. According to reports from the Walter Reed Army Medical Center in Washington, D.C., sustained TBI is found in nearly a third of all returning soldiers who have combat injuries.

According to David Koos, chairman and CEO of Bio-matrix, "The objective of our proposal is to develop an effective ASC-based (adipose-derived stem cell) therapy for TBI. Specifically, we will substantially study the therapeutic effect of ASCs on TBI-associated brain ischemia and inflammation via intravenous administration or by intro-cerebral transplantation. It is plausible that our proposed study will pave the way for an ASC-based therapy for TBI, which hopefully will be much more feasible and safer than other stem cell-based approaches."

Headquartered in San Diego, Bio-Matrix Scientific Group is involved in the design and development of the next generation of medical devices and instrumentation including non-invasive bio-systems monitoring devices, adult stem cell cryogenics and instruments for tissue management. A wholly owned subsidiary of Bio-Matrix Scientific Group, Entest BioMedical is involved in the development of testing procedures for diabetes, and in the development of stem cell applications to diabetes and other diseases.

Every 15 seconds, throughout the world, someone suffers a brain injury. For people who suffer permanent brain injury, the average cost of lifetime care and rehabilitation is in the millions of dollars per person. According to one of the leading researchers in the field, Dr. Tracy McIntosh of the University of Pennsylvania School of Medicine, "Sadly, it is an epidemic that most people do not realize exists, and to date, there is no clinical treatment that can effectively treat the damage." Another leading researcher in TBI, Dr. Ronald Hayes, director of the University of Florida Brain Institute, concurs by stating, "Currently no effective treatment exists."

TBI affects more people than stroke or Alzheimer’s disease combined. It is the leading cause of death in Americans under the age of 45, and it is also the leading cause of long-term neurological disability in children and young adults. According to the website of the National Institute of Neurological Disorders and Stroke (NINDS), a division of the National Institutes of Health (NIH), "Traumatic brain injury is a major public health problem, especially among male adolescents and young adults ages 15 to 24, and among elderly people of both sexes 75 years and older. Children aged 5 and younger are also at high risk for TBI." The Brain Injury Association of America defines TBI as follows: "A traumatic brain injury is defined as a blow or jolt to the head or a penetrating head injury that disrupts the function of the brain. Not all blows or jolts to the head result in a TBI. The severity of such an injury may range from ‘mild’, i.e., a brief change in mental status or consciousness, to ‘severe’, i.e., an extended period of unconsciousness or amnesia after the injury. A TBI can result in short or long-term problems with independent function."

Also known as "acquired brain injury", or simply "head injury", TBI is a type of "neurotrauma" that has been estimated to occur in approximately 1.5 million people per year in the United States alone. Of those, approximately 1.1 million cases per year are considered mild and are treatable in hospital emergency rooms, while approximately 235,000 cases per year are considered moderate and result in extended hospitalization, and approximately 50,000 cases per year are fatal. These figures are believed to be conservative estimates, as the actual number of people who sustain TBIs but who do not seek medical treatment is unknown. According to the U.S. Centers for Disease Control and Prevention (CDC), there are currently more than 5.3 million Americans who are living with some form of long-term or lifelong injuries that were incurred from TBI.

Reliable global statistics for TBI do not exist, although the World Health Organization has issued the following statement on the subject: "Neurotrauma is a critical public health problem that deserves the attention of the world’s health community. Estimates of brain and spinal cord injury occurrence indicate that these injuries cause enormous losses to individuals, families, and communities. They result in a large number of deaths and impairments leading to permanent disabilities. Research has also shown that traumatic brain injury usually requires long-term care and therefore incurs economic costs to health systems. For this reason, many countries need to develop surveillance systems and conduct epidemiologic studies to measure the impact of neurotrauma among their people to guide the development of more effective preventive methods. A number of methods have already proven effective, such as the use of motorcycle helmets, head supports in vehicles or on sports equipment." Among members of the military who have been deployed to war zones, and also among reporters who are assigned to cover such wars, blasts are the leading cause of TBIs. For military medical personnel who may be involved in the triage, treatment, and transport of such combat-related injuries, a publication entitled "Guidelines for the Field Management of Combat-Related Head Trauma" is available from the Brain Trauma Foundation, at www.braintrauma.org. The guidelines were compiled by a group of civilian and military experts from the fields of neurosurgery, trauma and EMS who were assembled by the Brain Trauma Foundation for the specific purpose of formulating such guidelines that would address the particular nature of war-related head injuries. The publication was funded by the Defense and Veterans Brain Injury Center in collaboration with the Henry M. Jackson Foundation for the Advancement of Military Medicine. Among the civilian population of the U.S., approximately half of all TBIs are caused by motor vehicle traffic accidents, and approximately half of all TBIs involve the use of alcohol. Outside of war zones, therefore, TBIs are among the most preventable of injuries. Between the ages of 15 and 24, males are nearly twice as likely as are females to sustain a TBI. For people aged 75 and older, most TBIs are the result of falls. Approximately 20% of all TBIs are due to violence, and approximately 3% are the result of sports injuries. Over 90% of TBIs that are caused by the use of firearms result in death, whereas approximately 11% of TBIs that are caused by falls result in death. As of 1995, combined direct medical expenses and indirect costs such as lost productivity from work due to TBI was estimated at $56.3 billion in the United States.

Adult stem cell therapy offers the first type of treatment for TBI which can actually heal the injuries by regenerating damaged neurological tissue.

(Please see the related section on this website, entitled, "Traumatic Brain Injury", located under "Research").

In response to President Obama’s March 9th Executive Order, the U.S. National Institutes of Health (NIH) have issued the first draft of a set of guidelines suggesting how federal funds should, and should not, be used for human embryonic stem cell research. The scientific, medical and religious communities have eagerly awaited the release of these guidelines, which have been highly anticipated, and debated, by all.

Specifically, the guidelines state that federal funds may now be used for research conducted on any human embryo that is “stored” at an IVF clinic and which is considered to be “spare”, “left-over”, or “orphaned”, after having been originally created at an IVF (in vitro fertilization) clinic for reproductive purposes. In other words, researchers may now apply for NIH grants to pay for such research – NIH grants being one of the primary, though certainly not the only, source of biomedical research funding throughout the United States. Nevertheless, contrary to public misconception, the NIH guidelines still prohibit the use of federal funds for research conducted on human embryonic stem cells derived from human embryos that were created by other means and for other objectives, such as, for example, somatic cell nuclear transfer, parthenogenesis, therapeutic cloning, and in vitro fertilization specifically designated for research or experimental, not reproductive, purposes.

It has been estimated that approximately 500,000 human embryos are currently frozen in a state of perpetual “limbo” in freezers at IVF clinics throughout the U.S., and many people, including the legal parents of these frozen “orphaned” embryos, are wondering what should be done about the situation. If any of the embryos were to be implanted into the uterus of an adult human female, many of the embryos would develop into a normal fetus and would ultimately be born as a human child, although some percentage of the embryos would either fail to implant properly or would fail to develop normally and would therefore not result in a healthy birth. When a woman solicits the services of an IVF clinic, usually for reasons pertaining to infertility, in order to be implanted with an embryo that was created through in vitro fertilization, it is standard procedure for the doctors of the IVF clinics to create multiple embryos with the IVF technique, precisely because of the fact that not every embryo will successfully implant and develop into a normal, healthy birth. The consequence of this routine, unquestioned practice is the creation of an unseen population of approximately half a million human embryos that nobody wants and which are destined either to be frozen indefinitely, discarded as biological trash, or now, as a result of the new NIH guidelines, deliberately destroyed in the process of embryonic stem cell research. The ethical can of worms that has been unleashed merely by the fact that these “orphan”, frozen human embryos exist, is beyond the scope of this news article to address, and possibly even beyond the scope of NIH to address. However, certainly one of the topics which NIH has yet to define precisely are the legal terms and conditions of the consent forms that parents of these frozen embryos must sign before their embryonic offspring can be officially designated for laboratory research and destruction.

Regardless of the specific legalities, embryonic stem cell scientists will now be allowed to receive federal funding (i.e., from NIH) for research which they may now perform on any of these “orphan” human embryos that are available from IVF clinics, all of which were originally created for reproductive purposes in the hopes of creating a human child, but which are “no longer needed for that purpose,” according to NIH acting director Dr. Raynard Kington. Although there are approximatley half a million orphaned human embryos frozen in IVF clinics across the U.S., it has been estimated that only approximately 700 new stem cell lines from those embryos would now be available for human embryonic stem cell research. Certainly 700 represents a significant increase from the number of human embryonic stem cell lines that were initially available in 2001 for federally funded research under the Bush administration, which originally had been estimated in the 60s but later proved to be numbered in the 20s. It is a common misperception, however, that President Obama has made broad, sweeping changes that will suddenly allow for any type of human embryonic stem cell research, as this is not the case, or at least not yet. The creation of human embryos specifically for research, not reproductive, purposes, is precisely what embryonic stem cell scientists covet the most, yet the federal funding of this type of research still remains illegal under the Obama administration, at least so far. Many proponents of adult stem cell research fear, however, that even this policy may, in time, change.

The new NIH guidelines allow for federal funding to be used for the very thing that is banned by the Dickey-Wicker Amendment, namely, research in which the health or life of a human embryo is threatened or destroyed. Although many people expect the Dickey-Wicker Amendment to be formally overturned at some time during the Obama administration, these NIH guidelines represent a concrete and immediate step in that direction. If Congress does, in fact, rescind the Dickey-Wicker Amendment, then the legalization of therapeutic cloning and other scientifically dangerous as well as ethically controversial procedures are seen as the logical next step. According to bioethicist Wesley Smith, “The political campaign has begun to destroy the Dickey Amendment. Should that happen, it would be legal for the Feds to fund human cloning, the making of embryos for research, and just about anything ‘the scientists’ wanted to do in this regard. Once that happens, the NIH would likely revise these guidelines to permit funding for those activities… Expect the struggle over Dickey to erupt within the next few years during the annual budgetary process. And if a bill passes sans the Amendment, there is no question in my mind that Obama would sign it.”

President Obama’s March 9th Executive Order directed NIH to submit guidelines addressing both the scientific and the ethical concerns of human embryonic stem cell research, within 120 days of that Executive Order, and NIH has issued this eagerly-awaited first draft in slightly over a month. According to NIH acting director Dr. Kington, “We considered the range of ethical issues and we believe this policy will allow the substantial research that is ethically responsible and scientifically worthy. We believe this is our best judgment now about a reasonable policy at this time.”

Apparently, a number of people disagree with Dr. Kington, such as, for example, Tony Perkins, president of the Family Research Council, who states, “The NIH draft guidelines demanded by the President will do nothing to advance stem cell research that is showing near-term benefit for suffering patients. Instead of funding more embryo destructive research, the government should fund research using adult stem cells that are on the cutting edge of treating patients for diabetes, spinal cord injury, heart disease and various cancers. Unfortunately, this draft guidance only diverts limited federal resources to unethical stem cell research that has not successfully treated a single person for any disease.”

Although embryonic stem cell proponents like to think that Obama’s policy on expanding embryonic stem cell research is a sign of “progress”, already Obama’s embryonic stem cell policy would appear to be outdated. It was nearly two years ago, on September 21st of 2007, that Dr. James Thomson was quoted in the Boston Globe as stating, “The world has changed. Over time, these [iPS] cells will be used in more and more labs. And human embryo stem cell research will be abandoned by more and more labs.” Dr. Thomson, of course, was the first person ever to isolate an embryonic stem cell in the laboratory, first in 1995 from a nonhuman primate and then in 1998 from a human. The entire field of embryonic stem cell research exists, therefore, purely as a result of Dr. Thomson’s achievements, and his name is revered in stem cell laboratories throughout the world. If anyone would understand the future direction of embryonic stem cell research, it would be Dr. Thomson. By sharp contrast to embryonic stem cells, the recently developed iPS (induced pluripotent stem) cells hold much greater research and clinical potential than do embryonic stem cells. Furthermore, since iPS cells can be created without involving an embryo at all, let alone destroying an embryo, iPS cells do not involve any of the ethical dilemmas that are inextricably entangled in embryonic stem cell research. Additionally, Dr. Ian Wilmut, who created the world’s first cloned mammal, Dolly the sheep, was quoted in Time magazine in December of 2007 as stating, “Changing cells from a patient directly into stem cells has got so much more potential”, once again referring to the advantages of iPS cells when compared to embryonic stem cells. Along those same lines, Dr. Shinya Yamanaka, who first developed iPS cells, was quoted in the December 11th, 2007 issue of the New York Times as stating, “We can’t keep destroying embryos for our research. There must be another way.” Apparently, neither President Obama nor the distinguished scientists at NIH have sought the advice of any of the world’s foremost leading authorities on embryonic stem cell research, cloning, nor iPS cells.

As stated on the website of the NIH, “The purpose of these draft Guidelines is to implement Executive Order 13505 on March 9, 2009, as it pertains to extramural NIH-funded research, to establish policy and procedures under which NIH will fund research in this area, and to help ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable law. Internal NIH procedures, consistent with Executive Order 13505 and these Guidelines, will govern the conduct of intramural NIH research involving human stem cells.” This first set of guidelines by NIH is only a draft, which will be published next week in the Federal Register where public comments from the general population will be accepted for the next 30 days. As also stated on the NIH website, “The National Institutes of Health (NIH) is requesting public comment on draft guidelines entitled ‘National Institutes of Health Guidelines for Human Stem Cell Research’ (Guidelines).” Apparently, members of NIH believe that it is possible for scientific and bioethical matters to be decided democratically, by majority opinion. Based upon the input of these public opinions, NIH is then expected to issue a final set of guidelines by early July.

(Please see the related news articles on this website, entitled, “Former Director of NIH Explains Why Embryonic Stem Cells are Obsolete”, dated March 4, 2009; “Obama Decrees Changes in Embryonic Stem Cell Research, Though Not What One Might Expect”, dated March 9, 2009; “Obama Rescinds Bush-Era Executive Order Pushing for More Ethical Stem Cell Research”, dated March 10, 2009; “Obama Signs Law Restricting Federal Funding of Embryonic Stem Cell Research”, dated March 11, 2009; “A High-Profile Proponent of Embryonic Stem Cell Research Sharply Criticizes Obama’s Policy”, dated March 13, 2009; and “Members of The President’s Council on Bioethics Object to Obama’s Stem Cell Policy”, dated March 26, 2009).

Known as the “Family Cord Blood Banking Act”, new federal legislation in the United States will amend the I.R.S. (Internal Revenue Service) Code to allow couples and individuals to use “tax advantaged dollars” in order to pay for the banking of umbilical cord blood and the adult stem cells contained therein. Tax advantaged financial accounts such as FSAs (flexible spending accounts), HRAs (health reimbursement arrangements) and HSAs (health savings accounts), and variations thereof, will now be applicable to cord blood banking expenses.

The legislation was introduced yesterday in the U.S. House of Representatives by Ron Kind (D-WI), Artur Davis, (D-AL), Wally Herger (R-CA), Mike Thompson (D-CA) and Bill Pascrell Jr. (D-NJ). According to Representative Ron Kind, the chief sponsor of the legislation and a member of the House Ways and Means Subcommittee on Health, “This legislation supports families that choose this potentially life-saving investment by providing tax incentives for these medical expenses.”

A number of private companies have announced that they support the legislation, including the Cord Blood Registry (CBR), which offers collection and preservation services of adult stem cells derived from umbilical cord blood. Currently, families are arbitrarily restricted by tax laws in the use of tax advantaged dollars and in the tax deduction of medical expenses. According to David Zitlow, senior vice president of public affairs and communications at CBR, “Families may pay for over-the-counter cough syrups or heartburn pills using these dollars, but not cord blood banking services. These limitations are unfair and even unwise. Families who opt to deposit into tax advantaged health accounts should have the discretion to spend those dollars as they see fit on qualified medical expenses.”

According to Dr. David Harris, the scientific director at CBR and a stem cell researcher at the University of Arizona, “Research and clinical trials involving cord blood will require more children to have a source of their own cord blood stem cells available for transplant. Consequently, legislation that makes it easier for families to bank cord blood will definitely speed up the time-table for life-saving research and will allow scientists to unlock the vast potential of these amazing cells on a much quicker basis.”

According to Matthew Schissler, CEO and founder of Cord Blood America, an international umbilical cord blood stem cell preservation company, “This would allow individuals and couples to pay for umbilical cord blood banking services through health savings accounts, flexible spending accounts, medical expense tax deduction and health reimbursement arrangements.”

Numerous organizations are involved in raising the awareness of, and lowering the financial barriers to, adult stem cell therapies derived from cord blood. In addition to CBR, other groups who have announced their support of the Family Cord Blood Banking Act include the Coalition for Regenerative Stem Cell Medicine and their member associations which include the Brain Injury Association of America (BIAA), the Association of Nurse Practitioners in Women’s Health, the Parent’s Guide to Cord Blood Foundation, and the National Spinal Cord Injury Association (NSCIA), among others, as well as a growing list of other foundations, companies, university institutions, researchers and disease advocacy groups.

Umbilical cord blood has a history of clinical therapeutic use that predates World War II, and adult stem cells derived from umbilical cord blood have been used in over 14,000 transplants in the treatment of more than 70 different diseases just in the past 20 years alone. While donating to a public cord blood bank is free, private cord blood banking carries associated expenses which may be as high as $2,000 for the first year and $125 for each year thereafter. The advantage, of course, is that the donating family retains the right of exclusive access to their stem cells that are stored in private banks, whereas those who donate to public banks relinquish the right to any future access to their own stem cells. Now, however, the new legislation will lower the cost to families through the new tax incentives, which not only will allow more people to benefit from private cord blood banking but it should also increase the overall supplies of cord blood stem cells.

The harvesting of adult stem cells from umbilical cord blood is a safe and non-invasive procedure which begins with the simple collection of umbilical cord blood at the time of birth. The adult stem cells may then be used throughout the future not only as a therapy for the person who donated the cord blood, but also as a therapy for biological relatives of that person, and for anyone for whom such stem cells may be immunologically compatible.

The Cord Blood Registry (CBR) is the world’s largest stem cell bank. The company is involved exclusively in the collection, processing and storage of adult stem cells derived from umbilical cord blood for future medical use. CBR was the first family cord blood bank to be accredited by the AABB (the American Association of Blood Banks). CBR has been cash-flow positive since 1999 and has thus far stored and processed the umbilical cord blood of more than 260,000 newborns from around the world.

The stem cell company Stempeutics Research has received approval from the Drug Controller General of India (DCGI) to begin the first clinical trial ever to be conducted in India with human stem cells. Specifically, the clinical trial will use mesenchymal stem cells derived from bone marrow in the treatment of two separate conditions, acute myocardial infarction and critical limb ischemia.

According to Nagendra Swamy, the Chief Operating Officer of Manipal Hospital in Bangalore, “It will be a multi-centric placebo-controlled, double blind and allogeneic clinical trial. The aim is to address two diseases: acute myocardial infarction and critical limb ischemia. Since [adult stem cells] derived from a single donor can be manufactured to treat 10,000 patients, we expect the product will provide affordable treatment for all.”

The global market for stem cell therapy is projected to reach $20 billion by the year 2010, and currently the stem cell therapy market in India alone is estimated at $540 million.

In addition to myocardial infarction and critical limb ischemia, which is an advanced form of peripheral artery disease, Stempeutics is also currently developing adult stem cell therapies for the treatment of Parkinson’s disease, spinal cord injury, motor neuron disease, end-stage liver disease, various skin disorders and avascular necrosis.

Aaron Cathcart was told by his doctor that he barely had a year to live, because his heart was so weak that he would not be able to survive surgery. That was over two years ago.

On June 26th of last year, however, Mr. Cathcart received autologous adult stem cell therapy in which his own adult stem cells, derived from his own bone marrow, were administered directly into his heart during open-heart surgery. Prior to receiving the therapy, his heart had an ejection fraction of less than 20%, whereas a normal ejection fraction range is considered to be between 55% and 75%. Three months after receiving the adult stem cell therapy, his ejection fraction had improved to 36%, and by January it had improved even further to 41%. Now, he no longer needs a defibrillator and is almost within the normal range for a healthy ejection fraction.

As Mr. Cathcart now describes, “It used to be that I couldn’t walk a couple hundred feet in the yard without getting pains. I couldn’t go out if the weather dropped below 50 degrees because my heart would strain in the cold.”

Since stem cell therapies are still plodding their way through the multi-year, highly expensive and lethargic FDA clinical trial process that is required for government approval of such therapies in the U.S., most stem cell therapies are not yet available in the U.S. at all, except through FDA-approved clinical trials. In fact, this is exactly how Mr. Cathcart discovered the therapy, since he was fortunate enough to find a clinical trial with adult stem cells that was being conducted not far away from his hometown. The company TCA Cellular Therapy was seeking patients who had suffered heart attacks but had never undergone heart surgery, conditions which applied to Mr. Cathcart and which made him eligible to participate in the trial. The therapy utilized autologous adult stem cells which were taken from each patient’s own bone marrow, expanded in the laboratory and then administered back to each patient according to his or her particular medical condition. Although such therapy usually eliminates the need for surgery, in Mr. Cathcart’s particular case the doctors determined that heart surgery was necessary due to the advanced pathology of his heart, so his own adult stem cells were injected directly into the dead tissue of his heart during bypass surgery.

Embryonic stem cells were never used in the therapy, due to the numerous medical risks and dangers that embryonic stem cells pose, not the least of which is the formation of teratomas (tumors). By sharp contrast, adult stem cells pose no such risks.

As Mr. Cathcart explains, “People hear ‘stem cells’ and they think ‘killing babies’. People are not distinguishing between the two. These were my own stem cells they used. Everyone’s body has them, and if you increase them in concentration, they can repair your body much better than normal.”

The company TCA Cellular Therapy, which is headquartered in Covington, Louisiana, is focused exclusively on the research and development of adult stem cell therapies, not embryonic stem cell therapies. Their latest successes in the treatment of various cardiac conditions hold great promise for the safe, effective and ethical treatment of diseases that afflict a growing number of people each year. In 2005 alone, it was estimated that over 35% of all deaths in the United States were related to cardiovascular disease, and every day approximately 2,400 Americans die from complications of this “silent killer”. Additionally, over 6 million people in the U.S. alone are believed to have blood-flow problems to their legs, which is a contributing factor to cardiovascular disease.

TCA Cellular Therapy owns two patents for proprietary autologous adult stem cell processes and products that are derived from the patient’s own bone marrow, and currently the company is in four separate FDA-approved Phase I and Phase II clinical trials, for the use of autologous bone marrow-derived stem cells in: 1/ the treatment of infarcted myocardium during bypass surgery, 2/ the non-surgical rescue and repair of cardiac muscle following acute myocardial infarction, 3/ the treatment of severe limb ischemia and 4/ the treatment of severe coronary ischemia. Further clinical trials for spinal cord injury and ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease) are still pending FDA review, and future protocols are currently being designed for the treatment of Parkinson’s disease and idiopathic cardiomyopathy with autologous adult stem cells.

During a conference call for institutional investors held Monday by Summer Street Research Partners, an independent health care research firm, a spinal surgeon and stem cell researcher offered a negative and cautionary view of Geron’s research. Subsequently, TheStreet.com decided not to disclose the doctor’s name due to privacy concerns, “since the call was not intended for public dissemination.” The doctor stated, however, that he has no financial ties to Geron, nor does he own, nor has he shorted, any of Geron’s stock. Nevertheless, the doctor pointed out that the highly publicized upcoming clinical trial for which Geron recently received FDA approval is clinically dubious because the entire rationale for the study is “based on a single experiment in 8 rats.”

In a highly controversial ruling, the FDA granted approval to Geron in January of this year to begin the first clinical trials ever to be conducted in the U.S. with human embryonic stem cells. The clinical trial will administer human embryonic stem cells to patients who have been paralyzed from the waist down with spinal cord injury. Since the primary objective of Phase I clinical trials is to test safety, efficacy will not be tested until years later – assuming, that is, that safety can be proven, although this remains the subject of widespread speculation. Without concrete evidence of safety, the proposed therapy cannot advance to further clinical trials.

In the days immediately following the FDA’s announcement, Geron’s stock soared from $5 a share to more than $48 a share, but such dramatic gains were quickly sold and the stock has steadily fallen ever since then, plummetting to a low of $3.79 on March 5th. According to Adam Feuerstein of TheStreet.com, “Even President Obama’s lifting of the federal research ban on stem cell research Monday failed to provide more than a marginal lift to Geron’s stock price, which closed Tuesday at $4.27”, up a mere 1.4%.

As Mr. Feuerstein further explains, “Wall Street’s health care investors, most notably biotech-focused hedge funds, have been more inclined to steer clear of Geron or short the company’s stock. Geron’s short interest has risen from 8 million shares to 17 million shares over the first two months of the year. Conference calls for Wall Street health care investors with experts critical of Geron’s research, like those held by Summer Street Research on Monday, explain why. The doctor on the Summer Street conference call, a spinal cord injury expert who has also conducted stem cell research, was skeptical about Geron’s study because there is very little animal data to support the theory that a therapy derived from [embryonic] stem cells will benefit patients with severe spinal cord injury.”

Indeed, as the doctor stated, “The fact that Geron’s entire study hinges on this one experiment in eight moderately injured rats is tenuous in terms of efficacy.”

This laboratory experiment upon which Geron’s upcoming clinical trial is based, was conducted by Dr. Hans Keirstead of the University of California at Irvine, using 8 rats in whom spinal cord injury had been deliberately inflicted in order to induce hind-leg paralysis. Rats that were treated with Geron’s human embryonic stem cell product saw a partial return of some function to their paralyzed legs after 7 days, but all of the rats were considered to have “moderate” spinal cord injury. However, when the start of treatment was delayed for more than a week, and also when the experiment was conducted on rats with severe spinal cord injuries, Geron’s therapy had no effect. The human patients who will participate in Geron’s clinical trial will not have moderate spinal cord injury, but instead they will have been chosen for the clinical trial because they suffer from severe spinal cord injury.

According to the doctor who spoke during the conference call, “We don’t know what will happen when these cells are placed into a human, which is the reason immune suppression is required. The risk is that these are not patients you would otherwise want to have on immune suppressants because the severity of their spinal cord injuries, the trauma they’ve suffered, their surgery and wounds make them more susceptible to infection.”

In Geron’s upcoming Phase I clinical trial, human embryonic stem cells will be injected directly into the spinal cords of the human patients. Ordinarily, after undergoing any type of transplantation, immune suppression is required for the remainder of the patient’s life, but the patients in Geron’s clinical trial will be removed from immunosuppressive drugs after 42 days, at which time there is a high risk of immune rejection by the patients’ bodies to the stem cells. In and of itself, this type of immune rejection has the potential to be life-threatening. As Mr. Feuerstein adds, “Another safety concern is the risk that the cells in Geron’s therapy may grow uncontrollably and form tumors on the spinal cord,” to which the doctor from the conference call further adds, “If one patient gets a tumor from the Geron therapy, it will be catastrophic.”

While the CEO of Geron, Tom Okarma, has tried to downplay expectations of efficacy by reminding the public that none of the patients are expected to be instantly cured from the Phase I clinical trial, it is a bit more difficult to dispel concerns about safety.

Despite the fact that Geron’s preclinical data is based upon only one experiment with only 8 rats, Geron’s FDA application nevertheless included a staggering 22,000 pages of data. Although such an unwieldy number might impress those who are uninitiated in “the scientific method”, Mr. Feuerstein points out that such an enormous FDA application “has not stopped some experts from questioning Geron’s science.” One such expert is Dr. Evan Snyder of the California- and Florida-based Burnham Institute for Medical Research, who wrote in an article that was published in the January 30th issue of the journal Science that, “There’s a lot of debate among spinal cord researchers that the preclinical data itself doesn’t justify the clinical trial.” Similarly, in the January 23rd edition of The New York Times, Dr. John Kessler, a neurologist and director of the Stem Cell Institute at Northwestern University, wrote, “We really want the best trial to be done for this first trial, and this might not be it.”

As every investor knows, financial markets are forward-looking, and the price of any particular stock at any particular time is a measure of confidence in that company. In Geron’s case, as with all other biotechs, the financial details are inextricably tied to the scientific details. Precisely for that reason, therefore, at least at this particular moment in history, institutional investors are growing increasingly wary of Geron because of the serious words of caution that are echoed throughout the medical and scientific communities.

An Israeli boy who suffers from a rare, often fatal genetic disease known as ataxia telangiectasia (A-T) has developed a tumor that was directly traced to the fetal stem cell therapy that he received. No known cure exists for A-T, which causes degeneration of the brain regions that control movement and speech, and people with the disease usually do not survive past their teens or twenties. Consequently, when the boy was 9 years old, his family traveled to Moscow so that he could receive an experimental therapy consisting of intracerebellar and intrathecal injections of human neural fetal stem cells – derived from aborted human fetuses – which were then injected into the boy’s brain and spinal cord as a treatment for his A-T. Even though he received two more treatments with the fetal stem cells at the ages of 10 and 12, he still had not shown any improvement by the age of 13 and in fact the severity of his disease had progressed to such an extent that he required a wheelchair. When he began having headaches, tests conducted at the Sheba Medical Center in Tel Aviv revealed a multifocal brain tumor pressing against both his brain stem and his spinal cord, which biopsy revealed to be a glioneural neoplasm. The tumor was surgically removed in 2006 when the boy was 14 years old, at which time cytogenetic and molecular analysis of the tumor revealed it to be of the same tissue as the fetal stem cells, and was therefore caused directly by the fetal stem cell therapy. Among other tests, genetic analysis revealed that some of the cells of the tumor had originated from a female donor and were comprised of 2 normal, healthy copies of the gene in which mutations cause the A-T disease, and which therefore did not match the boy’s own genotype containing abnormal copies of the gene.

Had this tumor not been discovered and surgically removed, it certainly would have been fatal and the boy would have died – not from the A-T disease, but from the therapy which was meant to treat the A-T disease. Indeed, one of the most serious concerns with embryonic and fetal stem cells is that they might constitute “therapies” which are worse than the diseases that they are meant to treat. This particular example with a boy suffering from A-T offers strong evidence to justify exactly such a concern. The boy is being closely monitored for any other tumors which might also possibly develop over time, as a lingering yet direct result of the fetal stem cell therapy that he received.

The formation of tumors has long been one of the main concerns associated with embryonic and fetal stem cells, and the fact that this boy’s tumor was not detected until 4 years after his first treatment raises some new concerns. According to Dr. Marius Wernig of Stanford University, “Stem cell transplantations have a humongous potential. But if people rush out there without really knowing what they’re doing, that really backfires and can bring this whole field to a halt.”

As Josephine Quintavale of the public interest group Comment on Reproductive Ethics adds, “The risks of tumor formation in association with embryonic stem cells are widely acknowledged and one reason why there are very serious concerns about the proposed use of such cells in treating spinal cord injury in the US. It would appear from this report that fetal stem cells are similarly unstable. These are not areas of therapy we should be rushing into, whatever the ethical debates surrounding the use of embryo or fetal tissue per se.”

Dr. Stephen Minger of King’s College London further explains, “This is worrying and we have to be cautious. We need to have long term monitoring and follow-up of the patients who are given stem cells and rigorous regulation of centres providing cell therapy. Although this is just one case, it does show that we need to be careful about the cell population we are using.”

As we have often explained on this website, all stem cells are not created equal, nor do they behave equally, and important distinctions must be made between the different types of stem cells. Generally speaking, all stem cells fall into 2 broad categories: adult stem cells, and everything else. The latter category includes embryonic and fetal stem cells, while stem cells that are derived from umbilical cord and placental blood are categorized as “adult” stem cells. The relatively recently discovered endometrial regenerative cells (ERCs), which have shown to be particularly promising, also fall into the category of “adult” stem cells. It is important to understand that adult stem cells behave very differently from embryonic and fetal stem cells, with one of the major differences being the risk of tumor formation, which has long been known to be inherently problematic in embryonic and fetal stem cells, especially in regard to the formation of teratomas (a specific type of tumor), which is the definitive requirement of pluripotency; by sharp contrast, however, adult stem cells do not cause tumors because adult stem cells are not pluripotent, but are instead multipotent, at best. In the past, the lack of pluripotency in adult stem cells was seen as a disadvantage, although increasingly it is being recognized as a distinct advantage, since it eliminates any danger of tumor formation.

According to a warning issued by Dr. John Gearhart, a stem cell scientist at the University of Pennsylvania, “Patients, please beware. Cells are not drugs. They can misbehave in so many different ways, it just is going to take a good deal of time.”

Although this particular case of tumor formation was originally reported in the PLoS medical journal, a peer-reviewed open access journal published by the Public Library of Science, the story was subsequently republished in all major media outlets around the world. As the authors of the PLoS paper cautiously conclude, “This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.”

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.

Neuralstem Inc. announced this morning that it has filed an IND (investigational new drug) application with the U.S. FDA (Food and Drug Administration) to begin the first ever human clinical trials for the treatment of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, with adult stem cells.

According to Richard Garr, J.D., president and CEO of Neuralstem, “Like all first human trials, this proposed trial is primarily designed to test the safety and feasibility of both our stem cells and our method of delivering the cells to the spinal cord in ALS patients. We are also proposing secondary endpoints which we hope will be able to measure a slowing down of the degenerative process.”

The treatment will consist of spinal injections of the adult stem cells using the company’s patented and proprietary technology. The clinical trials will take place at Emory University under the direction of Dr. Johnathan Glass, Director of the Emory Neuromuscular Laboratory and Director of the Emory ALS Center, pending offical FDA authorization.

Approximately 30,000 people in the U.S. alone are afflicted with ALS, which is a progressive neurodegenerative disease in which the deterioration of nerve cells and motor neurons progresses from a loss of muscular control to paralysis and ultimately death. Conventional medical modalities have thus far been unsuccessful in halting or reversing the course of the disease, which until now has been considered incurable. Adult stem cell therapies, however, constitute the first type of treatment that is actually capable of offering realistically achievable improvement.

According to Richard Garr, “The filing of this IND is an important event for Neuralstem, but it marks only the beginning of a process which includes working together with the FDA to approve the first human ALS stem cell trial, refining our understanding of how to optimize delivery of our cells into patients, and ultimately delivering a new treatment for patients with this currently incurable disease.”

As described on their website, “Neuralstem, Inc. is a publicly traded biotherapeutics company whose mission is to apply stem cell research and its patented human neural stem cell technology to treat diseases of the central nervous system including ischemic paraplegia, traumatic spinal cord injury, ALS and Parkinson’s disease. Our stem cell research has resulted in patent-protected technology that allows us to produce mature, commercial quantities of neural stem cells with the ability to control the differentiation of the cells into physiologically relevant human neurons and glia.”