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Stem Cells Show Promise for Parkinson's

Study in mice, rats raises hope for therapy without fetal cells

TUESDAY, Jan. 8, 2002 (HealthDayNews) -- Embryonic stem cells transplanted from mice into the brains of rats that have the equivalent of Parkinson's disease become dopamine-producing neurons and restore lasting motor function, a new study says.

The researchers say the findings raise hope of someday transplanting human embryonic stem cells into patients with Parkinson's disease, rather than relying on donor fetal brain tissue, which is both controversial and hard to obtain in sufficient quantities.

The findings appear in the Jan. 8 issue of the Proceedings of the National Academy of Sciences.

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

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

One such surgery involves transplanting cells from the midbrain of human fetuses. Between three and eight midbrains are required per procedure, with each midbrain containing about 400,000 dopamine-producing cells.

However, while the procedure helps approximately half of those who undergo it, only 10 percent of the implanted cells survive the procedure in even the best scenarios. It also treads on ethically shaky ground because many people oppose the use of fetuses.

The lead investigator of the newest study, Dr. Lars Björklund, says that previous studies had suggested that embryonic stem (ES) cells, unless they are nudged to become some other type of cell, will automatically become neurons.

Björklund and his colleagues in Massachusetts and Stockholm suspected that it was not necessary to transplant large numbers of ES cells. In transplants involving 50,000 to 100,000 ES cells, they thought, the cells in the center of the transplanted tissue never interact with the new environment, and thus don't develop into cells suited for that part of the body.

The researchers decided to transplant small numbers of mouse ES cells into 25 rats. Another 13 rats, acting as controls, underwent similar surgery in which they didn't receive the stem cells.

The grafts did not survive in six of the rats, and five animals were euthanized after they developed masses of many cell types at the transplant site. But in 14 rats, the transplant worked, producing functioning dopamine neurons.

"You can get dopamine neurons that function when injected into the brain, even without any specific manipulation," says Björklund. "It's a combination that they become neurons on the default pathway and then we put them in a place where it's beneficial for dopamine neurons to be because they can establish contacts."

The contacts, he says, may provide the neurons with nutrients that support their specific cell types. "The dopamine neurons may survive a little better in this environment compared to other neurons," he adds.

Björklund found that the newly functional dopamine neurons reduced the rats' uneven motor function. Functional magnetic resonance imaging scans also revealed that rats that received ES cell grafts produced dopamine in response to an injection of amphetamine, while animals that didn't receive the ES cells showed no such response.

The researchers then looked at eight of the 14 rats that got the transplant. Five of them experienced either reduced jerky movements or no worsening of their condition.

The results weren't perfect, points out Dr. Curt Freed, the director of the Neural Transplant Program for Parkinson's Disease at the University of Colorado Health Sciences Center in Denver.

About 20 percent of the ES cell graft animals developed unwanted, non-neural cells that grew uncontrollably in the brain. But even that is an advance, says Freed, because in previous studies using large-scale transplants, this type of growth was almost universal.

"It says that if you inject just a small number of cells, then the cells are more influenced by their immediate environment, and are more likely to become more appropriate cells for the brain," says Freed.

Björklund hopes that this finding could lead to a technique that avoids the use of fetal cells. "We saw a behavioral recovery that is comparable to what we see with fetal transplants," he says. "Using embryonic stem cells, we have a possibility of getting cells that would work as well as fetal cells."

But he stresses that while these results are promising, clinical trials in humans are still between three and seven years away.

What to Do: 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.

SOURCES: Interviews with Lars Björklund, M.D., Ph.D., instructor, Neuroregeneration Laboratory, Department of Psychiatry, McLean Hospital, Belmont, Mass.; Curt R. Freed, M.D., professor and head, Division of Clinical Pharmacology and Toxicology, Departments of Medicine and Pharmacology, and director, Neural Transplant Program for Parkinson's Disease, University of Colorado Health Sciences Center, Denver; Jan. 8, 2002, Proceedings of the National Academy of Sciences
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