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Monkey Stem Cells May Ease Parkinson's

Scientists, using higher mammal, convert them to dopamine neurons

MONDAY, Jan. 28, 2002 (HealthDayNews) -- Taking an important step forward in treating brain diseases with stem cell therapy, Japanese scientists say they've converted embryonic stem cells from monkeys into dopamine factories.

A dearth of dopamine is the cause of Parkinson's disease, and in earlier work the scientists quickly generated neurons that produced the messenger molecule from mouse stem cells. Since primates are much more closely related to people, experts say the latest work brings the approach nearer to human patients.

Dr. Curt Freed, director of the Neural Transplant Program for Parkinson's Disease at the University of Colorado Health Sciences Center, calls the Japanese study "an important milestone."

"Discovery of a practical way to convert stem cells into dopamine neurons is essential to make neurotransplantation available to large numbers of Parkinson's patients," Freed says.

The findings appear in the Feb. 5 issue of the Proceedings of the National Academy of Sciences.

Parkinson's disease is a progressive neurological disorder that disrupts the brain's control of motor functions. The disease, which results from the death of neurons that produce dopamine, affects approximately 1.5 million Americans and millions worldwide.

Patients suffer from worsening tremors, stiffness, slow movement and balance problems. The disease also interferes with the ability to walk, talk and perform other routine tasks. Although some medical and surgical therapies exist for Parkinson's disease, it has no known cure.

Stem cells have shown promise in effectively reprogramming diseased brains, at least in lower animals. These supple, primitive cells are capable of becoming virtually any tissue in the body.

Previously, the Japanese researchers discovered they could generate brain cells from mouse embryonic stem cells by using a technique they called "stromal cell-derived inducing activity," or SDIA. Stromal cells make up connective tissue. By using them as a culture for stem cells, the scientists fostered the birth of dopamine neurons. How the combination works isn't certain, but it appears to involve some yet-unidentified growth factors the stromal cells secrete.

In the latest work, a team led by Hiroshi Kawasaki, a medical embryologist and neurobiologist at Kyoto University, applied the same technique to stem cells culled from embryos of cynomolgus monkeys, a common research species. When mixed with the stromal cells, the tissue created neurons, 35 percent of which began producing dopamine.

The researchers grafted some of the dopamine neurons into the brains of mice whose own dopamine-related cells had been depleted. After two weeks, roughly 8 percent of the grafted tissue was still viable and had begun to grow. The scientists say they are trying to repeat that experiment in monkeys to study how long the transplanted neurons can survive.

In a surprising twist, Kawasaki's group says the experiment also generated eye cells called pigmented epithelia. These act as support staff for the rod and cone cells that sense light.

"The SDIA method provides an unlimited source of primate cells for the study of [illness], drug development and transplantation in degenerative diseases such as Parkinson's disease and retinitis pigmentosa," the researchers write. The latter condition is a leading cause of inherited night and total blindness.

Dr. Su-Chun Zhang, a stem cell expert at the University of Wisconsin-Madison, says the mystery of SDIA isn't significant from a practical perspective. However, it will be important to determine how the process is so good at teasing out neurons from stem cells.

"Even [they] themselves do not know how it works," Zhang says.

Not every researcher, however, is keen on the concept of cell grafts for Parkinson's.

Arnon Rosenthal, founder and president of Rinat Neuroscience Corp., a California-based biotech company, says experimental transplants of fetal cells have been disappointing so far in humans.

"Even in the best cases, transplants can ameliorate only part of the symptoms," Rosenthal says. For example, grafts won't ease tremors because they don't reconstitute the original dopamine system, acting instead as an overlay. That's because the heart of the dopamine system sits in an area of the brain that controls critical body functions, including breathing, and surgeons are afraid to go near it, he explains.

Although monkey tissues would likely be a better fit for people than cells from mice or pigs, Rosenthal says primates' proximity to humans raises the serious threat of cross-contamination with harmful viruses.

For these reasons, Rosenthal, who is familiar with the Japanese group's work, believes preventing Parkinson's and other neurodegenerative disorders is a better strategy. Not surprisingly, his company is working on drugs to do just that.

What To Do

The National Institutes of Health has a primer on stem cells, as does the American Association for the Advancement of Science.

For more information on Parkinson's disease, check out the National Institute of Neurological Disorders and Stroke, the Parkinson's Disease Foundation or the National Parkinson Foundation.

In addition, for more on retinitis pigmentosa, try RP International.

SOURCES: Interviews with Curt Freed, M.D., director, Neural Transplant Program for Parkinson's Disease, University of Colorado Health Sciences Center, Denver; Su-Chun Zhang, M.D., Ph.D., professor of anatomy and neurology, University of Wisconsin-Madison; Arnon Rosenthal, Ph.D., founder, president and chief technology officer, Rinat Neuroscience Corp., Palo Alto, Calif.; Feb. 5, 2002, Proceedings of the National Academy of Sciences
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