First stem-cell patient reports feeling in legs

The first patient to receive a human embryonic stem-cell treatment for paralysis from a spinal-cord injury says he has regained some feeling in his legs.

Timothy Atchison of Alabama, 21, partially paralyzed in a Sept. 25 car crash, told the Washington Post that he's begun to feel slight sensation where there was no sensation before -- for example, a sense of relief when a bowling ball is lifted from his lap, or discomfort when he pulls on hairs on his legs.

While the report is anecdotal and is not scientifically verified, Hans Keirstead, the UC Irvine stem-cell researcher who invented the treatment used on Atchison, said he was nevertheless thrilled by the news.

"It's an extraordinarily exciting outcome," Keirstead said. "One that is very hopeful for the treatment."

But Keirstead cautioned that it is far too early in the treatment's clinical trial to draw conclusions about its effectiveness.

"His impressions are not going to have a bearing on the outcome of the trial," Keirstead said.

Keirstead is not involved in the trial and has not spoken to Atchison.

The young nursing student was the first patient to be injected with stem cells in the world's first clinical trial of a human embryonic stem-cell treatment.

The treatment is for acute spinal cord injuries, so the treatment must take place within 14 days of the injury. It involves injection of neural cells derived from human embryonic stem cells; those are taken from embryos otherwise destined to be discarded by fertility clinics, but the treatment still generates controversy among those opposed to use of such cells.

The trial is being conducted by Geron Corp. at the Shepherd Center in Atlanta, Ga., one of seven potential sites around the country where the clinical trial will be held.

Patient identities are secret, but Atchison came forward to speak to the Post.

The first stem-cell trial is, in keeping with normal practice, focused on testing the safety of the procedure and patient tolerance.

The treatment's effectiveness will be evaluated in a future trial.

"I'm an eternal optimist," Keirstead said. "I absolutely expect individuals in the phase 1 clinical trial to provide anecdotal evidence that the treatment might have some benefit.

"You have to understand, I'm extremely biased: I developed it. When I put my scientific hat on, I try to disregard as best I can this anecdotal evidence, and wait patiently for the formal outcomes of the clinical trial."

Those outcomes won't be known, he said, until two years after the last patient is treated.

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'Landmark' neural stem cell trial underway

A US company has launched an experimental neural stem cell clinical trial for patients paralysed by spinal injury. StemCells Inc will extract neural stem cells from donated aborted fetuses to be injected into the spines of patients with chest-level spinal cord injury.

Dr Armin Curt, Medical Director of the Paraplegic Center at the Balgrist University Hospital, will lead what he believes to be a 'landmark trial' designed to administer the experimental therapy. 'For patients facing a lifetime of paralysis, the prospect that neural stem cell transplantation may one day help restore some degree of function offers new hope', Dr Curt said.

Dr Stephen Huhn, vice-president and head of the central nervous system programme at StemCells Inc told the Times last week: 'We are hoping to see incremental improvement that could well improve quality of life. It might be improvement in motor function, but it could be as simple as improved bladder or sexual function'.

Fetal neural stem cells have already differentiated, or been 'programmed', to generate into any of the central nervous system cell types. This makes them distinct from undifferentiated embryonic stem cells, which have the potential to become any cell type in the body.

Animal studies demonstrated that, when fetal neural stem cells are injected into the spines of paralysed animals, they can produce new specialised cells that help regenerate function without causing tumours or other adverse results. In particular, they were found to turn into oligodendrocytes, which regenerate nerves' protective myelin sheaths that commonly become damaged by injury.

British patients may apply to participate in the trial, but overall numbers are limited. Three groups of patients with different degrees of injury will be enrolled to take part in the trial. The first group will include patients who have no movement or feeling below the area of injury, the second will include patients who have some feeling below the injury, and the third group will include patients who experience some movement. Twelve patients in total will take part.

Dr Curt, who will monitor patient safety and therapeutic efficacy, is excited by the 'innovative design' of the trial, which 'will progress from the most severely injured to less severely injured' enabling the opportunity to observe a range of mechanisms for potential benefits.

The trial differs from another US spinal cord clinical trial begun in California last year by rival company Geron, which applies human embryonic stem cells to patients with new spinal cord injuries. The StemCells Inc trial is believed to be the first to use fetal neural stem cells applied to older injuries, sustained three to 12 months beforehand.

Each patient group will be assessed over one year with an additional four-year observation period following completion of the trial. 

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Stem Cell Researchers at UM Embark on New Trial

Stem cell researchers at the University of Miami Miller School of Medicine’s Interdisciplinary Stem Cell Institute are preparing to embark on another research milestone. Joshua M. Hare, M.D., professor of medicine and director of the Interdisciplinary Stem Cell Institute (ISCI), has received approval from the U.S. Food and Drug Administration to begin the first clinical trial in the nation comparing autologous stem cells to donor stem cells for patients with dilated cardiomyopathy, a condition that causes congestive heart failure and is a major cause of death and disability.

Dilated cardiomyopathy directly causes weakness of the heart muscle, a condition that can be very severe and lead to heart failure. It can be caused by viral infections, genetic disorders, inflammation or in many cases the cause is unknown. Patients are treated with medication which can sometimes improve heart function, but some patients’ hearts continue to deteriorate and require heart transplantation or other advanced therapies.

ISCI investigators are already studying a number of stem cell types in clinical trials for patients with heart muscle damage from a prior myocardial infarction (heart attack). This new study is the first to examine whether stem cells may also prove beneficial for other forms of heart muscle weakness, and will compare the effects of autologous cells (stem cells derived from a patient’s own bone marrow) with allogeneic cells (stem cells from an adult donor). Enrolled patients with dilatedcardiomyopathy will be injected with either their own stem cells or cells from a pre-screened healthy donor.

“This trial will answer major questions about the treatment of heart failure, and could transform treatment of these patients,” Hare says. “Cell therapy for this condition could reduce the need for heart transplantation and other advanced therapies by providing a viable alternative. Also, using donor cells could make this potential new therapy highly practical and easy to deliver.”

While there is quite a bit of excitement about the potential healing ability of stem cells, Hare explains that there is also concern that stem cells taken from a patient who is already ill may be compromised and weakened because of that illness. “This study will help us find out if a heart failure patient’s stem cells are already damaged and not as effective. If so, the availability of donor cells could be life-saving to these patients.”

The ability to safely and effectively use a donor’s cells could also provide physicians with a nearly unending supply of these potentially healing cells. Using autologous cells is a time-consuming process. Physicians must first extract a patient’s bone marrow, containing mesenchymal stem cells. Once those mesenchymal cells are separated, they must be cultivated in a lab to enhance their numbers – a process that takes up to six weeks. For some heart failure patients, waiting that long for an effective treatment may not be feasible. “If we can prove that donor cells work as well or better than autologous cells without any negative side effects,” says Hare, “that will open up many new doors for us when it comes to new therapies.”

Currently, Hare is leading three other stem cell trials for patients with heart failure due to heart attack or myocardial infarction at the Miller School. The first, which began in April 2008, is a double-blind, placebo-controlled study in which doctors are injecting either the patient’s mesenchymal stem cells or a placebo into the heart during surgery. The two additional studies deliver cells to patients by catheter, avoiding a surgical procedure.

In the new clinical trial, dubbed POSEIDON-DCM, scientists will use one or two young, healthy donors who have been thoroughly screened for any communicable diseases. Once those donors are recruited, their cells can be cultivated in the lab to grow numerous batches for use in this trial.Mesenchymal stem cells are immunoprivileged, meaning there is no need for any matching process between the donor and the recipient. Immune suppressive drugs are not required, and rejection has not been seen in heart failure patients treated thus far with donor stem cells.

Alan W. Heldman, M.D., professor of medicine, leads the team that injects stem cells directly into the heart muscle. In the new POSEIDON-DCM trial, Stem Cell injections will be done with the NOGA® electroanatomic navigation system, which allows the cardiologist to guide injections into specific sites in the heart based on the electrical and mechanical function at that site. “In the other trials we’re conducting, we have already gained an enormous amount of experience with the techniques of injecting stem cells into patients’ hearts,” says Heldman. “This study may add tremendously to the state of knowledge about whether and how stem cells can truly help regenerate stronger heart muscle.”

Another key member of the ISCI team, Juan Pablo Zambrano, M.D., assistant professor of medicine, agrees that the study will provide a better understanding of the role of stem cells in cardiac repair. Zambrano hopes the trial will “show an option for an even larger heart failure population that suffers from conditions other than heart attacks.” He says the study will also expand their expertise in new imaging modalities that help locate weakened areas of the heart as targets for cell administration.

William O’Neill, M.D., executive dean for clinical affairs, describes this new trial as “another milestone for the university of Miami’s Interdisciplinary Stem Cell Institute.” He says Hare and his colleagues are taking a leadership role in stem cell therapy for heart disease, and the poseidon -DCM trial will “further our understanding of which cells are most likely to repair damaged heart tissue.”

This trial is a key step forward for the team, says Ian McNiece, Ph.D., professor of medicine and director of experimental and clinical therapies at ISCI. “This study will provide important information relating to the types of heart disease that can be repaired by mesenchymal stem cells.”

The external scientific advisory board of ISCI recently concluded that the institute is the leading translational stem cell program in the U.S. and that the cohort of patients treated for cardiac disease is the largest in the nation. The board’s report said the “complement of trials being offered at UHealth broadens the availability of experimental therapy to patients and offers an alternative to the growing trend of medical tourism for cell based therapies.”

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Researchers pioneer clinical trial of embryonic stem cells

For the first time, researchers are using embryonic stem cells in a clinical trial to treat patients with spinal cord injuries. The trial strives to test whether these cells can be safely used to treat humans.

This initial investigation of embryonic stem cells stands apart from prior trials, which have all relied on adult stem cells. If successful, it may be expanded to larger clinical trials.

Geron Corporation, a Menlo Park-based company that develops cellular technology, sponsored the trial. Overall, the trial may enroll up to 10 patients with spinal cord injuries in seven locations across the country.

The Stanford School of Medicine and Santa Clara Valley Medical Center, collaborating together, constitute the third clinical site for the trial. Cells will be grown at Stanford, while surgeries will be administered at the Valley Medical Center.

At Stanford, Gary Steinberg, professor of neurosurgery, and Marco Lee, clinical assistant professor of neurosurgery, have been authorized to implement the new treatment.

“We are very excited about this trial,” Lee said. “This trial marks the first FDA-approved, clinical, phase-one embryonic stem cell trial. If this initial clinical trial proves to be safe, the FDA will approve further trials with a larger patient pool.”

“Most of the people involved would be overjoyed if there is no adverse reaction,” Steinberg said.

Adding to the excitement is the fact that Stanford and Santa Clara are two of a limited number of institutions that will have the opportunity to carry out this research.

“Stanford is the only site west of the Mississippi,” Steinberg said. “Geron was very selective who got invited to participate.”

Northwestern University is the only other site that has been officially identified by Geron. The company has yet to disclose information on the five remaining sites.

The company wanted facilities that could rigorously carry out the clinical trial and provide the necessary medical support for participating patients. The medical centers need to be equipped to take care of patients with spinal cord injuries.

The clinical trial recruits patients who recently suffered a trauma or blunt injury to the thoracic region of the spinal cord, which stretches from the top of the shoulder blades to the bottom of rib cage. The patients qualify as paraplegic because they have lost motor abilities from the waist down, including bowel control. The participants have usually been in car accidents and have experienced a crushing fracture to the spine.

Individuals with penetrating wounds, such as bullet or knife wounds, are not qualified to enroll in the study. Researchers have been able to use embryonic stem cells to repair blunt spinal injuries in animal models, but not penetrating spinal injuries.

To participate in the trial, a patient must notify his doctors and request to opt-in within seven to 14 days of his injury.

“This requires patients to come to terms with their condition and request for the new procedure,” Lee said. Finding suitable participants for the trial can be difficult, because many patients fully cannot come to terms with their situation within two weeks of their traumatic accidents.

Since the clinical trial is currently in its preliminary stages, there are still no conclusive results. Researchers do not know if there will be adverse reactions, such as tumor formation, from the injection of stem cells into the spinal cord. Positive animal model results are not easily transferable to humans.

But scientists remain hopeful.

“There is a lot of excitement about this, but there is a lot of caution,” Steinberg said. “Advances in medicine are made in small steps, not quantum leaps. That being said, we’ve never had something like this before.”

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FDA lifts hold on first human embryonic stem cell trial

Geron Corporation (Nasdaq: GERN) announced that the U.S. Food and Drug Administration (FDA) has notified the company that the clinical hold placed on Geron's Investigational New Drug (IND) application has been lifted and the company's Phase I clinical trial of GRNOPC1 in patients with acute spinal cord injury may proceed.

The FDA notification enables Geron to move forward with the world's first clinical trial of a human embryonic stem cell (hESC)-based therapy in man. The Phase I multi-center trial is designed to establish the safety of GRNOPC1 in patients with "complete" American Spinal Injury Association (ASIA) Impairment Scale grade A subacute thoracic spinal cord injuries.

The hold was placed just several months after the FDA first approved the trial in January 2009 following results from a single preclinical animal trial, which found that animals developed small cysts within the injury site in the spinal cord. The prevalence of cysts was higher in this trial than previous studies, the company said. Geron developed new markers and assays, or blood tests, and completed another preclinical animal study before submitting a request the FDA to lift the hold. 


The Phase I clinical trial will test the drug's (GRNOPC1) safety in human patients. The drug contains hESC-derived oligodendrocyte progenitor cells that have shown remyelinating and nerve growth stimulating properties, leading to restored function in lab animals with acute spinal cord injury.

The company's therapy uses various growth factors to turn embryonic stem cells into precursors of the neural support cells (oligodendrocytes). These are then injected into the spinal cord at the injury site. If the therapy works, the injected cells will help repair the insulation around the nerve cells, which could restore the ability of some nerve cells to carry signals. And it's possible that the growth factors produced by the injected cells could help damaged nerve cells to regenerate.

"Our goals for the application of GRNOPC1 in sub-acute spinal cord injury are unchanged -- to achieve restoration of spinal cord function by the injection of hESC-derived oligodendrocyte progenitor cells directly into the lesion site of the patient's injured spinal cord," said Dr. Thomas Okarma, the company's president and CEO, in prepared remarks.

The company is also looking into using the therapy in other illnesses, including Alzheimer's, multiple sclerosis and Canavan disease, Okarma said. 


Source: Geron Corporation

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