March 25, 2009 by

Growing New Cartilage With Your Own Adult Stem Cells

Researchers in Edinburgh, Scotland are developing a new medical procedure that “knits together” torn knee tissue with autologous adult stem cells. The technique will be tested in clinical trials with patients within the next year.

The research is being led by Dr. Anthony Hollander of Bristol University, who was a member of the U.S. team that successfully reconstructed a new trachea last year with autologous adult stem cells in the treatment of then 30-year-old Claudia Castillo, who received a new trachea that was grown from her own adult stem cells. (Please see the related news article on this website, entitled, “New Trachea Grown from Autologous Adult Stem Cells”, dated November 26, 2008, and originally reported in The Lancet).

Now, a similar procedure will offer a new form of therapy for injuries and degenerative conditions that are common to the knee. Although the new technique is targetted specifically for the repair of tears in the meniscus, which is a part of the knee cartilage in which sports injuries are especially common, the treatment will also offer relief to the many individuals who suffer from osteoarthritis.

Speaking at a conference of the Scottish Stem Cell Network in Edinburgh yesterday, and in reference to tears in the miniscus, Dr. Hollander stated, “At the moment, there’s no way to treat this. It is just cut out, and that leaves the patient very susceptible to osteoarthritis within a short number of years.” One such example is Alan McLaren, a former defender first for the Heart of Midlothian team and later for the Rangers, who was abruptly forced to end his professional sports career in 1999 at the age of 27 after suffering a cruciate ligament injury. Clearly, Mr. McLaren could have benefited from such a therapy, and he might have been able to continue his highly successful football career, had this type of stem cell therapy existed a decade ago.

The upcoming clinical trials will initially enroll 10 patients, in whom adult stem cells that have been grown on a membrane will be implanted directly into the lesions of their knees, and sewn up. As Dr. Hollander explains, “It is designed in a way that the cells will migrate across the lesion and literally knit it together. So instead of growing new tissue, it’s healing the lesion itself.”

Only autologous adult stem cells will be used in the clinical trial, derived from each patient’s own bone marrow.

A number of other researchers in Scotland are planning similar clinical trials, including Dr. Brendon Noble of the Centre for Regenerative Medicine at Edinburgh University, whose focus will be more oriented toward age-related osteoarthritis rather than sports injuries.

Meanwhile, Dr. Hollander is also developing further improvements in trachea transplants that are re-engineered with adult stem cells and grown in the laboratory, the technology for which is also believed to be applicable to the regeneration of other organs, including large blood vessels and the intestine.

Filed Under: News, Osteoarthritis, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 20, 2009 by

Old Dogs Learn New Stem Cell Tricks

Once again, veterinarians are healing canine injuries with adult stem cell therapy. This time, the vets and their four-legged patients are in Australia.

Veterinarians in Sydney are applying an already proven technique to the treatment of injuries and degenerative diseases in dogs. The technique, which was first developed in the U.S. by the company Vet-Stem, uses autologous adult stem cells derived from the adipose (fat) tissue of each dog to treat the dog of joint and bone injuries as well as age-related osteoarthritis. Already successful in other countries, the technique is now also showing great success in Australia.

According to Dr. Ben Herbert, associate professor at the University of Technology in Sydney and director of the University’s Proteomics Technology Centre of Expertise, “What we see is a pretty rapid, within the first couple of days, reduction in the animal’s pain and inflammation. We see animals that are a lot happier, then you go into a zone where the science tells us we are actually getting new cartilage. Longer term, going out now to the dogs treated 9 and 10 months ago, those dogs are still improving.”

One such example is Cassie, a 12-year-old border collie mixture whose favorite activity now involves chasing small wild animals. However, prior to receiving the adult stem cell therapy, Cassie suffered from severe osteoarthritis of the hips, and even slow walking was painful for the dog. According to Elizabeth Beyer, Cassie’s owner, “Before, going for a walk would be a bit of an ordeal. Now we can do a walk any day of the week. Her hips have improved, she’s walking faster. She chases possums and whatever else comes into the garden. It’s about quality of life.”

The treatment, which has been available at the Ku-Ring-Gai Veterinary Hospital in Sydney for less than a year, has already been used to treat 60 dogs in Australia, whose owners travel with the dogs from across the country to receive the therapy. Although the treatment is initially more expensive than conventional veterinary medicine, the benefits are also greater. Dramatic, positive results are seen immediately after receiving adult stem cell therapy, and the dogs usually do not need any further treatment of any type. Like Cassie, many other dogs who received the autologous adult stem cell treatment have also been cured of their ailments and no longer require long-term anti-inflammatory drugs nor painkillers, most of which do not offer a cure but in fact carry dangerous side effects and, over time, are considerably more expensive than the adult stem cell therapy. From a long-term perspective, therefore, the adult stem cell therapy is actually less expensive than conventional veterinary treatments, such as surgery and medication, which are not as effective and may need to be repeated throughout the dog’s life.

As Dr. Herbert explains, “These are the patient’s own cells. It’s effectively a transplant and it’s this idea of switching on the body’s own regenerative system.” Since the adult stem cells are autologous (in which the donor and recipient are the same dog), there is no risk of immune rejection, nor is there any need for the use of dangerous immune-suppressing drugs.

Overall, the procedure is quick, simple, minimally invasive, safe, effective, and less expensive than surgery or taking prescription medication for years. Although this type of adult stem cell therapy has already become quite popular in other countries such as the U.S., a number of independent researchers have published corroborating evidence throughout the medical and scientific literature on the safety and efficacy of such a therapy.

Currently, Dr. Herbert and his colleages are also developing a similar autologous adult stem cell treatment for dogs with kidney disease. As he explains, “This has given us the opportunity to immediately translate early-stage research into the clinic and get real clinical data. It’s on dogs and cats, but it’s in the real world.”

As Dr. Herbert further explains, “There is nothing really different about doing that in a human being and doing it in a dog.” He is quick to add, however, “The regulatory regime is easier to deal with in dogs.”

Indeed, it seems to be much easier for old dogs to learn new tricks, at least when it comes to adult stem cell therapy, than for the respective government regulatory agencies of various countries to do so.

Filed Under: News, Osteoarthritis, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 19, 2009 by

Adult Stem Cell Therapy for Diabetes Shows Progress

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

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

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

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

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

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

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
March 18, 2009 by

Teeth as a Form of Health Insurance

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

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

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

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

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

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

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

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

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
March 18, 2009 by

Growing a New Heart With Adult Stem Cells

Some species have a natural capacity for regenerating large quantities of their tissue whenever they suffer damage, the ultimate example of which is the salamander, in which spontaneous regrowth of entire limbs and even of large parts of its heart and brain have been well documented. Similarly, the popular aquarium resident, the zebrafish, has also been found to be capable of regrowing entire pieces of its heart, whenever necessary, due either to unfortunate accident or to the deliberate experimentation of curious humans. In any case, and regardless of the species, such regeneration is possible because of naturally occurring, endogenous, adult stem cells which exist within the organism precisely for this very reason: namely, to wait patiently until activated by injury or illness, at which time the adult stem cells valliantly come to the rescue to repair and replace damaged or missing tissue. However, biological regeneration is generally believed to be inversely proportional to evolutionary complexity, so that, in other words, the more biologically advanced a species is, the less natural regenerative ability that species possesses, and vice versa. Such a theory would explain why, for example, regeneration of entire limbs and organs is spontaneously seen in amphibians and fish but rarely in humans or other mammals.

However, such a theory may be incorrect.

Generally considered (at least by themselves) to be the most highly evolved and advanced species on the planet, human beings are now showing a natural ability for biological regeneration, at least at a cardiovascular level.

In developed countries such as the United States and Canada, cardiovascular disease continues to rank as the number one cause of death, and conventional medical therapies which consist of surgical procedures in combination with pharmaceuticals have not offered a satisfactory treatment for the disease and its numerous complications. Now, adult stem cells offer the first actual therapy which is capable not only of restoring full function to the damaged heart but also of regrowing healthy heart tissue; and such therapies are most successful when they work in combination with the body’s own reservoir of endogenous adult stem cells.

Dr. Christopher Glover, an associate professor of medicine at the University of Ottawa and a cardiologist at the University of Ottawa Heart Institute, has been conducting a clinical trial in which endogenous adult stem cells are activated in patients following a heart attack. The clinical trial consists of 86 heart attack patients to whom a proprietary “drug” was given which activates the migration of each patient’s own endogenous adult stem cells from the bone marrow into the bloodstream, from which the stem cells then automatically “home in” on, and target, the damaged tissue of the heart. As Dr. Glover describes, “There are some repairs that our bodies can [automatically] do. If we amplify the response, perhaps we’d get more repair.” This treatment is meant to amplify the body’s natural response mechanisms, and although the clinical trial is still in progress and has not yet concluded, the patients are already improving “even better than expected”, according to Dr. Glover.

A similar study was conducted last year in an animal model in which an organic, collagen-based gel was injected directly into damaged tissue in laboratory rats and was subsequently found to stimulate angiogenesis, which is the formation of new blood vessels. The use of various agents, including externally derived stem cells, to stimulate naturally occurring endogenous adult stem cells is a popular and widely validated procedure that has been independently corroborated by a number of scientists in a number of studies conducted around the world.

The successful stimulation of the body’s own adult stem cells extends far beyond the cardiovascular realm, however, and has already been applied to a wide range of therapies that require much more than mere angiogenesis. In fact, even in humans, a number of sources have documented the natural ability of the body’s own adult stem cells to repair damaged tissue, even without external stimulation. For example, in human children prior to the age of approximately 10 years, the regrowth of entire fingertips that have been lost in accidents has been reported, as long as the wound is not deliberately sealed with a skin flap, which, unfortunately, is the usual de facto emergency treatment that is administered to such accidents, and which reliably prevents the natural regrowth of the finger by the artificial physical barrier that it creates. Without such physical barriers, however, and with a more enlightened medical approach, regrowth of digits is not uncommon in humanns. A particularly remarkable demonstration of such regeneration involved the case of Lee Spievack who, in his 60s, accidentally sliced off the end of one of his fingers in the propeller of a hobby shop airplane, after which he was treated with a powder that was applied directly to the injured area. Within four weeks, the missing half-inch of his finger completely regrew, including not only the flesh and blood vessels but also the bone and nail. The powder contained a proprietary extracellular matrix compound which stimulated and cooperated with the man’s own endogenous adult stem cells in regrowing his missing finger. Likewise, the U.S. Army has already been applying adult stem cell technology to the regrowth of limbs for wounded soldiers returning from Iraq and Afghanistan. (Please see the related news articles on this website, entitled, “Grow Your Own Replacement Parts” and “Growing Miracles”, dated February 6th and February 7th of 2008, respectively, each originally reported by CBS Evening News).

Regardless of the species, and across all species, the physiological body of each organism has a natural and strong genetic tendency to heal itself; even in humans, our very DNA is programmed to repair the cellular damage that results from the various injuries and illnesses of life. Regardless of the specific type of medical therapy that is used for any particular ailment, the greatest medical successes will result from those therapies that harness, to the fullest possible extent, the body’s own natural healing abilities. In the realm of stem cells and regenerative medicine, we are thus far only barely able to glimpse the tip of the iceberg.

As Dr. Marc Ruel, a cardiac surgeon at the University of Ottawa Heart Institute, puts it, "We know it’s going to work. We are living proof of it. Nature proves this concept every day."

Filed Under: Heart Disease, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 15, 2009 by

Heart Patients Report Dramatic Improvement with Adult Stem Cell Therapy in Clinical Trials

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.

Filed Under: News, Spinal Cord Injury, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 13, 2009 by

Common Enzyme Sheds Light on Health and Disease

Researchers at the Washington University School of Medicine in St. Louis report some interesting discoveries with the enzyme known as adenosine monophosphate-activated protein kinase (AMPK). Already known to be involved in a number of diseases, AMPK has been well studied by scientists for many years, but these new findings are the first of their kind to demonstrate that the enzyme is essential for the health of neural stem cells.

In a study led by Jeffrey Milbrandt, M.D., Ph.D., the researchers found that when they selectively deactivated the enzyme in mouse embryos, the overall brain size of each mouse shrunk by 50%, with dramatic shrinkage in both the cerebrum and the cerebellum to such an extent that the mice died within 3 weeks of birth. AMPK, it turns out, is a critical component for the survival of neural stem cells which in turn create and maintain the cells of the central nervous system, including the cells that are necessary for learning and memory. When AMPK is deactivated or absent altogether, normal neurological health cannot be maintained at the cellular level.

According to Dr. Milbrandt, “For years, scientists have shown how AMPK regulates multiple metabolic processes, and revealed how that influence can affect cancer, diabetes, and many other diseases. Now, for the first time, we’ve shown that AMPK can cause lasting changes in cell development. That’s very exciting because it opens the possibility of modifying AMPK activity to improve brain function and health.”

AMPK is directly involved in the regulation of cellular energy usage, and the enzyme is specifically activated whenever energy resources are low, such as during times of caloric restriction or sustained physical exercise. When activated, AMPK promotes cellular glucose uptake, mitochondria formation, fatty acid oxidation and other energy-producing cellular processes, while simultaneously inhibiting protein and fatty acid synthesis as well as cell reproduction and other energy-consuming cellular processes.

When activated, there is one particular version of AMPK that is capable of making its way into the nucleus of cells where it inactivates the retinoblastoma protein, “a master regulator” of cell production, which in turn allows neural stem cells to survive and proliferate. That particular version of AMPK, which contains the beta 1 subunit and which is only one of several versions of AMPK, is capable of penetrating both the cytoplasm and the nucleus of cells, whereas other versions, such as that which contains the beta 2 subunit, have only been found in the cytoplasm but never in the cell nucleus. As Dr. Biplab Dasgupta, a lead author of the paper, describes, “Inhibiting AMPK is something that most cells don’t like. It can lead to a variety of consequences, including cell death, but many cell types can tolerate it. In contrast, neural stem cells undergo catastrophic cell death in the absence of AMPK containing the beta 1 subunit. We also suspect loss of this form of AMPK may cause severe problems for other stem cells.”

Because of the role of cancer stem cells in some types of cancer, and the possibility of manipulating AMPK in cancer therapies, ideally the trick would be to inactivate AMPK in the cancer stem cells themselves, while simultaneously activating AMPK in the normal, non-cancerous cells.

Since the protein retinoblastoma, which the AMPK version with the beta 1 subunit regulates in the cell nucleus, plays such an important role in the differentiation of stem cells, these findings also have possible implications for the long-term health effects of malnutrion. According to a study that was conducted in 1977 on the children of women who were starved by the Nazis during World War II, these children remained at a high risk of various diseases throughout their lives, which included diabetes, heart disease and stroke. Even though these children, themselves, had never been subjected to starvation, their mothers may have incurred long-term damage to their stem cells as a result of their experiences, which in turn influenced the cellular health and development of their offspring.

On a lighter note, Dr. Dasgupta adds, “Exercise activates AMPK and improves cognitive function. Our results suggest brain function may improve because additional activated AMPK makes it easier for adult neural stem cells to reproduce and become new brain cells.”

As Dr. Milbrandt concludes, “Manipulating this regulation may enable us to encourage the development of new brain cells. We might use that not only to treat medical conditions where brain development is hampered, but also to improve cognitive function generally.”

Filed Under: Heart Disease, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 11, 2009 by

Geron Seen as Scientifically and Financially Risky

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.

Filed Under: News, Spinal Cord Injury, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 10, 2009 by

How to Mend a Broken Heart

Former heart patients such as Howard Lindeman and Dick Dufala are strong advocates of adult stem cell therapy, and their enthusiasm is the result of personal experience. Along with many other people who share similar stories, Mr. Lindeman and Mr. Dufala have adult stem cell therapy to thank for the fact that they are no longer in danger from the life-threatening heart conditions with which they had previously suffered.

According to Mr. Lindeman, who chose to undergo adult stem cell therapy follwing a heart attack, “It’s the most amazing thing I’ve ever been through. I had the procedure done and since then, I’ve just been getting better and better and better. I’m going to be 58 years old in May and I’m on my way to being 35 again.”

Similarly, according to Mr. Dufala, who used to suffer from congestive heart failure before receiving adult stem cell therapy, “I think it’s improved my life and my life will be extended as a result of having the procedure. I feel like I don’t have congestive heart failure. I feel quite good.”

Both men underwent their adult stem cell therapies from the cardiologist Dr. Zannos Grekos, who uses autologous (in which the donor and recipient are the same person) adult stem cells derived from each patient. Speaking at a seminar recently in Naples, Florida, Dr. Zannos explained, “Because it is coming from the patient, there’s no [immune] rejection and there’s no risk of cancer because we’ve been using adult stem cells for about 40 years in treating cancers. We know that adult stem cells are effective.”

By stating that “there’s no risk of cancer”, Dr. Zannos is referring to the fact that embryonic stem cells are defined by their ability to form teratomas (tumors), which is the formal scientific definition of pluripotency, whereas adult stem cells are not capable of forming such tumors for the simple reason that adult stem cells are not pluripotent. Similarly, in his statement that “we’ve been using adult stem cells for about 40 years in treating cancers”, Dr. Zannos is referring to the fact that bone marrow transplants have been conducted for several decades now, and the mechanism-of-action by which bone marrow transplantation is effective is through the adult stem cells that are present in the bone marrow. More specifically, the first bone marrow transplant was performed in 1956, which was over 5 decades – over half a century – ago. It was Dr. E. Donnal Thomas of Cooperstown, New York, who performed this first successful bone marrow transplant that resulted in the long-term survival of the patient who subsequently enjoyed a complete remission of leukemia after being given a bone marrow transplant from an identical twin. For this first, pioneering medical procedure, Dr. Thomas was awarded the Nobel Prize in Physiology or Medicine, along with Dr. Joseph E. Murray, “for their discoveries concerning organ and cell transplantation in the treatment of human disease.” This revolutionary transplantation paved the way for numerous other transplants of a similar nature, which in turn were followed in 1968 by the first bone marrow transplant from a related donor in the treatment of a non-cancerous condition, namely, in the treatment of a four-month-old boy who had inherited severe combined immunodeficiency syndrome. This procedure in turn opened the door for numerous other bone marrow transplantations for non-cancerous conditions, which in turn were also followed in 1973 by the first bone marrow transplant using an unrelated donor, which was performed at Memorial Sloan-Kettering Cancer Center in New York City and which likewise paved the way for numerous other procedures of a similar nature. It has therefore been for over the past 50 years that bone marrow transplantation has demonstrated the safety and efficacy of the adult stem cells that are present in bone marrow. If one were to trace the history of umbilical cord blood therapies, one would find that these therapies extend back even farther in time and predate World War II by at least a decade, and for over the past 70 years the various uses of the adult stem cells that are present in umbilical cord blood have been documented in the medical literature for the treatment of a vast number of people for a variety of conditions, without adverse side effects. Although the concept of a human stem cell, per se, was not yet understood at these times, prior to World War II nor even in 1956 when the first bone marrow transplant was performed, today it is well known and understood that bone marrow transplants and umbilical cord blood work as effective treatments because of the adult stem cells that they contain. By contrast, the first human embryonic stem cell was only isolated in the laboratory in 1998, so embryonic stem cell science is barely a decade old, and in that short decade embryonic stem cells have never been used to treat anyone for anything. A clinical history, therefore, does not exist, at all, for embryonic stem cells, which thus far can be said to have a 0% success rate, which is the equivalent of a 100% failure rate. Since embryonic stem cells carry a number of inherent risks, not the least of which is their strong natural ability to form teratomas (tumors), even the most ardent of embryonic stem cell proponents has cautioned that an actual therapy based upon embryonic, not adult, stem cells is at least another decade away, if such a goal is attainable at all. Meanwhile, there are many patients who cannot wait that long for treatment, and fortunately adult stem cells are already being used as clinical therapies to help such people.

In reference to the natural regenerative ability of the body’s own adult stem cells, even in full-grown adults, Howard Lindeman adds, “The people who doubt it should stop doubting because it is a fact that our body can heal itself. If it didn’t, I’d be dead right now.”

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 4, 2009 by

Former Director of N.I.H. Explains Why Embronic Stem Cells are Obsolete

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

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

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

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

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

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

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

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

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
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