The National Institutes of Health has awarded a Yale researcher $6 million to transplant neural cells in primates in an attempt to replace dopamine lost in Parkinson’s disease.

Transplantation of fetal neural cells was carried out on a limited basis in patients at Yale with mixed results, said D. Eugene Redmond, M.D., a professor of neurosurgery and psychiatry at Yale School of Medicine and principal investigator on the study. Two larger studies at other institutions have largely replicated the results of the Yale study, which was one of the earliest in the United States.

“In patients the functional improvement appears variable,” he said. “The procedure is less effective in older patients and incomplete in spite of some apparent increases in dopamine production.”

Redmond said transplantation’s limitations may result from inadequate grafts, poor survival of implanted cells, lack of critical growth factors, or nonphysiological graft placements and distribution.

He will utilize the five-year program grant to test these hypotheses with strategies that may improve functional benefits. Project One targets early cell death after grafting. Project Two will determine the benefits of combined methods of transplantation in young adult and aged primates. Project Three aims to restore the relevant dopamine pathways by implanting precursor tissue and directing its growth to target areas. Precursor cells are those that have not yet differentiated into a particular function, but are already genetically programmed to do so. Prior to studies in patients, these methods must be studied using fetal brain cells from monkeys in a model of Parkinson’s disease that can only be produced in monkeys (and has occurred accidentally in humans).

Redmond said understanding fetal precursor cell survival and outgrowth may also lead to improved understanding of the plasticity and function of other potential replacement cells, such as stem cells, and be relevant to other human neurodegenerative or traumatic conditions in addition to Parkinson’s disease.

“In spite of the enthusiasm for stem cells, their success may not be independent from the effects of fetal precursor cells, which are the present gold standard cell that stem cells should become,” he said.

He said further studies of fetal cell transplantation in animals and new studies in patients using the latest techniques are needed to understand how to replace lost and damaged cells and to cure the associated diseases. “When improved cells become available, the knowledge gained in this process will remain useful,” Redmond added. “There still is not a transplant cure that patients with intractable Parkinson’s disease can sign up for, but there has been enormous progress and the goal is in reach.”

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