Neurons implanted in stroke-damaged brain tissue show function, say University of Pittsburgh researchers

August 21, 2001

PITTSBURGH, Aug. 21 - An imaging study of neurons implanted in damaged areas of the brains of stroke patients in the hopes of restoring function has shown the first signs of cellular growth, say University of Pittsburgh researchers.

Positron Emission Tomography (PET) scans taken six months after surgery to implant LBS-neurons showed a greater than 10 percent increase in metabolic activity in the damaged parts of some patients' brains compared to scans taken just a week prior to surgery. The increased metabolism corresponds with better performance on standardized stroke tests for behavioral and motor function.

While PET scans taken at 12 months post-surgery showed that metabolism in the implanted area itself had lessened to baseline, the surrounding area in some patients showed maintained or even improved function - perhaps evidence that the LBS-neurons were becoming integrated into the brain.

Results of the study from the first human neuroimplantation trial for chronic stroke appear in the September issue of Neurosurgery.

"These changes in glucose metabolism in the stroke and surrounding brain tissue may represent cellular activity or grafting of the implanted neurons," said Carolyn Cidis Meltzer, M.D., associate professor of radiology and psychiatry and medical director of the University of Pittsburgh Medical Center's PET facility and principal author of the study. "Although this is not direct evidence of synapse formation, it does suggest that the new neurons are being wired into the brain."

Dr. Meltzer and her colleagues performed PET imaging on 11 patients who suffered strokes resulting in persistent motor deficits at least a week before, then six months after implantation surgery. Nine of the original group went through the scans again at 12 months. Metabolism was measured by the uptake of a glucose analog called fluorodeoxyglucose (FDG) by the cells.

After six months, increases of FDG greater than 10 percent were observed in seven of 11 patients. After 12 months, the increase was sustained by three of the 11. In the areas surrounding the stroke, only two of 11 patients showed a greater than 10 percent increase in metabolism at six months, but after a year, five of 11 patients had at least one scan demonstrating a rise in relative metabolism over baseline.

The increased metabolism correlated with positive changes in neurological evaluations (National Institutes of Health stroke scale, European stroke scale) given to the patients during a 52-week period following transplant.

Patients are all part of the first human trial of the effectiveness of neuroimplantation to repair damage caused by stroke. Principal investigators in the trial are Douglas Kondziolka, M.D., professor of neurological surgery and radiation oncology and Lawrence Wechsler, M.D., professor of neurology and neurosurgery, both of the University of Pittsburgh School of Medicine.

LBS-neurons originated from a human teratocarcinoma, a tumor of the reproductive organs that is composed of embryonic-like cells, which was removed from a 22-year-old cancer patient in the early 1980s. Layton BioScience Inc. has licensed a patented process that uses several chemicals to transform this cell line into fully differentiated non-dividing human neuronal cells that can be used in clinical applications. In extensive pre-clinical testing, implants of LBS-neurons reversed cognitive and motor deficits in animals in which stroke had been induced.

The implantation procedure begins with the placement of a stereotactic frame on the head of the patient. The frame is a standard tool in neurosurgery to provide a fixed way to find specific locations within the brain. The patient then receives a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and the surgical team makes its final decision for location of cell implantation.

Concurrently, the University of Pittsburgh Immunologic Monitoring and Diagnostic Laboratory team thaws the human neuronal cells that were frozen by and transported from Layton BioScience Inc.

After the cells are transferred to a long-needled syringe, the surgeon uses CT to guide their injection at multiple sites. The surgeon injects these cells through a small opening in the skull and patients leave the hospital the next day.

Stroke affects approximately 750,000 people in the United States each year and is the third leading cause of death and most common cause of disability.

There are no known effective treatments for chronic stroke with fixed neurological deficit.
Co-authors are Douglas Kondziolka, M.D.; Victor L. Villemagne, M.D.; Lawrence Wechsler, M.D.; Steven Goldstein, M.D.; Keith R. Thulborn, M.D., Ph.D.; James Gebel, M.D.; Elaine M. Elder, Sc.D.; Sharon DeCesare, M.D.; all of University of Pittsburgh and Alan Jacobs, M.D., of Layton BioScience Inc.

The study was funded by Layton BioScience Inc.

University of Pittsburgh Medical Center

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