“We have very little to offer patients with moderate to severe strokes after the four- and one-half hour treatment window for the clot buster tPA has passed,” said Dr. David C. Hess, stroke specialist and Chairman of the Medical College of Georgia Department of Neurology at Georgia Health Sciences University.
GHSU is one about 10 study sites for MultiStem®, a novel stem cell therapy developed by Cleveland-based Athersys, Inc., that may reduce stroke size and enhance patient recovery even if administered more than a day after symptoms begin. The stem cells can be used in conjunction with tPA for ischemic strokes, the 80 percent of strokes caused by oxygen deprivation in the brain, Hess said. tPA is currently the only Food and Drug Administration-approved drug therapy.
About 140 adults with a moderate to severe strokes resulting in movement and/or speech deficits will be enrolled nationally in the clinical trial; GHSU expects to enroll about 10 patients. Some participants will receive a placebo while others will receive a single, intravenous infusion of stem cells. Two different doses are being studied to assess safety and efficacy.
GHSU researchers have been studying the stem cells in animal models of ischemic stroke for about eight years.
Laboratory studies have shown the cells can reduce stroke size and damage by secreting nourishing trophic factors whose signals and growth factors help keep injured cells alive, reducing inflammation that targets injured brain cells and helping grow new blood vessels that re-establish blood and oxygen to the area. The cells also seem to reduce the spleen’s response to stroke, which is to send more immune cells to the brain where they can contribute to the damage. The stem cells do not seem to make new brain cells directly and few persist in the brain long term although the healing effects appear very durable based on preclinical studies.
Study participants will be followed for one year, receiving periodic blood tests to look for inflammatory factors and magnetic resonance imaging to look at stroke size. “We hope stem cell therapy will help patients get better and get better faster,” Hess said. For some patients, spontaneous recovery may happen within 24 hours of a stroke although many patients are left with long-term disabilities that dramatically reduce quality of life. Rigorous physical therapy also can aid recovery over many months.
Hess notes that tPA can deliver a “home run” for patients who get it early by busting up the problematic clot before it can do any real damage. However despite the fact that tPA was approved by the FDA 16 years ago, only 5-10 percent of patients receive it because of the narrow treatment window, which in 2009 was widened from three hours to four- and one-half hours after symptoms begin.
Hess said treatment with MultiStem® could occur in a more clinically practical timeframe, enabling a substantial improvement in quality of life, such as patients being able to walk unassisted or get around with a walker instead of being bedridden. “These are huge differences in quality of life,” said Hess who is collaborating with University of Georgia researchers to find even more options.
A study with Dr. Susan C. Fagan, Albert W. Jowdy Professor and Assistant Dean for the GHSU program of the UGA College of Pharmacy, is exploring the potential of an old intravenous antibiotic, minocycline, which may also inhibit the immune response that can destroy brain tissue and blood vessels.
Still in the laboratory stages are studies with Dr. Steve Stice, UGA stem cell researcher and Georgia Research Alliance Scholar in Reproductive Physiology, of artificially produced IPS cells, which can become any type of body tissue. While clinical trials of the IPS cells for stroke are likely five to10 years out, Hess hopes they will one day help patients whose brains have been irrevocably injured by stroke regain near normal function by growing new brain cells.
Patients interested in participating in the study may come to Georgia Health Sciences Health System Emergency Department following a stroke or call the Department of Neurology at 706-721-1691. Exclusionary criteria for the MultiStem® trial include severe heart problems, hypertension uncontrolled by medication and seizures following stroke.