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2004-2-11 14:06:00

NIH资助神经干细胞移植治疗研究

A Yale researcher was recently awarded $6 million from the National Institute of Health to study neural cell transplantation in primates to treat Parkinson's disease.

D. Eugene Redmond, M.D., and Yale School of Medicine professor of neurosurgery and psychiatry, is the principal investigator on the study. The five-year grant will enable Redmond to study the transplantation of cells into primate brains in an effort to reintroduce dopamine-producing cells to combat the effects of Parkinson's.

Parkinson's disease is a chronic, degenerative neurological disorder in which dopamine-creating brain cells die prematurely. Dopamine is a chemical messenger, transporting signals in the brain to control movement, a capacity compromised in patients with the disease. Parkinson's affects an estimated 500,000 to one million Americans.

Dr. Paul Sheehy, project director at the National Institute of Neurological Disorders and Stroke (NINDS) which is sponsoring Redmond's grant, said Redmond's research promises improvements over current, less effective Parkinson's treatments.

"In therapy we give [patients with Parkinson's] dopamine in various forms -- but it's only effective for five to seven years, and often before that, disabling complications come up," Sheehy said. "So of course, we would like to come up with a more effective therapy."

The research will be comprised of three main projects. The first will focus on ways to improve the survival of transplanted cells into the brain. The second project will focus on growth factors, proteins that bind to cells to activate cellular growth and differentiation, and that have been shown to aid cell survival in this research. The third project is related to implanting cells into their natural place in the brain, from which they will deliver dopamine to other areas.

"Almost all studies that have been done with transplanted cells for Parkinson's have put the cells in the place that they're supposed to deliver their transmitter substance, but not the place they ordinarily were before they were destroyed," Redmond said. "We're trying to put the cells in their original location."

Redmond said one difficulty of the study is that fetal precursor cells are hard to collect and their use is still controversial, as the cells are collected from deceased fetuses.

"It's very difficult to get the [fetal] tissue -- as well as the fact that though it's been resolved in the U.S. that this research is acceptable, there are still people opposed to it," Redmond said.

These issues have shifted attention to stem cell transplantation. Though both stem cells and fetal precursor cells are not yet differentiated into their particular functions when they are collected, stem cells still have the potential to develop into any cell type in the body. Precursor cells, however, are already genetically committed to develop into a certain cell type.

While stem cell transplantation has recently attracted much public attention, Redmond said procedures using fetal precursors cells are more successful at this time.

"[The difficulties of obtaining fetal tissue has] helped provide the rationale for the use of stem cells -- I also have another grant from the government to study stem cells, but the truth is we're a lot farther away from making those stem cells into dopamine neurons that we are with [fetal] precursor cells," he said.

The technology developed from these studies also holds the potential to treat other diseases.

"There is definitely the possibility that this type of work will be effective for a number of other conditions -- the replacement of the insulin secreting cells in the pancreas, with diabetes, for example," Redmond said. "This is a proof of principle for many other potential treatments."

Yale is prominent in research of this type. Redmond said the first successful transplant of fetal brain tissue to a primate was conducted at Yale in 1985. Yale also had a clinical program from 1989 to 1993 transplanting fetal brain tissue into human patients with Parkinson's. However, these transplantations were less successful, leading researchers to revert to animal subjects.

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