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Yale team assessing neural stem cells as a treatment for Parkinson’s disease

Yale Medicine Magazine, 2002 - Autumn


Researchers at Yale are about to embark on a series of experiments to determine whether human neural stem cells can cure Parkinson’s disease that has been induced in monkeys by a neurotoxin. Pilot studies have shown that these cells can be successfully integrated into the brains of fetal, neonatal, infant and adult monkeys for at least a month.

The experiments, funded by a $2.4 million grant from the National Institute of Neurological Disorders and Stroke, are designed to determine whether the stem cells, once integrated into the brain, will restore the production of dopamine. Parkinson’s results from unknown processes that kill dopamine cells, causing muscle rigidity, lack of coordination, difficulty moving and tremors. Primordial and uncommitted, neural stem cells can be propagated in large numbers and then safely differentiated into the necessary dopamine-producing neurons after they are injected into the brain. “Stem cells appear capable of becoming the appropriate replacement cells for the lost dopamine cells in Parkinson’s disease,” said lead investigator D. Eugene Redmond Jr., M.D., professor of psychiatry and neurosurgery. “This appears to happen spontaneously when they are implanted into the correct areas of the brain, and there are also known methods as to how to get them to do this in culture.”

Stem cells have certain advantages over fetal brain tissue, which Redmond used in similar research a decade ago. In those experiments Redmond and other researchers, relying on private funding, transplanted brain tissue from aborted fetuses into the brains of patients with Parkinson’s disease. They reported some initial success, but over the years outcomes were mixed. The progress of that research has been slow, with a major drawback being the difficulty of finding sufficient quantities of suitable fetal cells.

Unlike the fetal cells, stem cells divide in culture, so adequate amounts can be produced and they can be made of uniform quality and meet established safety levels.

“The human neural stem cells migrate to populate developing or degenerating brain regions, perhaps allowing a functionally correct and effective reconstruction,” said Redmond.

Federal funding for the research is permitted because the stem cell lines are derived from fetal-cadaver brain tissue, not embryos. Research involving embryonic stem cells remains controversial. Last year President Bush announced that federal funding would be permitted only for research involving embryonic stem cell lines derived prior to Sept. 9, 2001.

The project, to be carried out in conjunction with scientists from Harvard Medical School, the University of Colorado and the St. Kitts Biomedical Research Foundation, also seeks to test whether the cells will survive, differentiate and integrate into the brains of normal adult monkeys without immunological rejection or harmful overgrowth.

“These studies will advance our understanding of the neurobiology and safety of human neural stem cells in a well-established, clinically relevant primate model of Parkinson’s disease and, if successful, will support safe clinical studies in patients with Parkinson’s disease in the future,” Redmond said. “The results will also advance our understanding of useful methods for studying and treating a broad range of neurodegenerative, genetic and traumatic conditions of the nervous system.”