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Science News

Converting Cells Shows Promise for Parkinsonís

By Nicholas Wade

In a striking instance of biologists’ new prowess at manipulating human cells, researchers at the Whitehead Institute in Cambridge, Mass., have converted skin cells from people with Parkinson’s disease into the general type of neuron that the disease destroys.

The new approach, though it requires further work, would in principle allow the brain cells that are lost in Parkinson’s to be replaced with cells that carried no risk of immune rejection, since they would be the patients’ own.

The Whitehead scientists, reporting in Thursday’s issue of the journal Cell, said that the method worked in five patients whose skin cells were transformed in the test tube into neurons that produce dopamine, a chemical that transmits messages between neurons in certain regions of the brain. It is the loss of dopamine-producing nerve cells that leads to Parkinson’s symptoms, which can include muscle rigidity, tremors and slowed movement.

The immediate goal of the research, led by Frank Soldner and Rudolf Jaenisch, is to grow the dopamine-producing cells in the laboratory to seek the cause of the degenerative disease. The cells could be exposed to the various environmental toxins that have come under suspicion as possible contributory causes.

A longer-term goal is to prepare cells suitable for transplantation. The cells of a Parkinson’s patient presumably have some innate predisposition to the disease. But since the disease generally does not show up for 50 years or more, an infusion of a new batch of cells may give the patient more useful years.

The Whitehead team exploited a discovery made in 2007 by the Japanese scientist Shinya Yamanaka, who found that mature cells could be reprogrammed back to the embryonic state with surprising ease. The trick is to insert a handful of genes that are active in the embryonic cell, usually on the back of a virus because viruses are adept at delivering active genes into cells.

With the patients’ skin cells converted back to the embryonic state, the scientists used an established recipe for driving the embryonic cells down a different path. By exposing them to a sequence of factors, they converted the embryonic cells into dopamine-making neurons.

Another scientific team achieved this goal last year, but left the virus inside the cells. Virus-laden cells are unsuitable for transplant. The Whitehead team also found that the virus caused subtle differences in the cells’ activity. So they developed a way of snipping the virus out of cells once it had completed its mission. Their dopamine-producing neurons are free of the virus and the three extra genes required for reprogramming the skin cells.

Dr. Jaenisch said the real promise of the new approach was to provide Parkinson’s-type neurons that could be grown in the laboratory to study how the disease develops. “Before you get to patients, there are many issues to be resolved,” he said. “I would think therapy is pretty far away.” But he said generating transplantable cells was “doable” once technical problems were solved.

Dr. Fred Gage, a nerve cell expert at the Salk Institute in San Diego, called the new finding “a good technical advance,” but noted that the new dopamine-producing cells still contained a few DNA sequences left over from their construction, even after the virus and the three genes had been snipped out.

Dr. Anders Bjorklund, a pioneer in using cell therapy to treat Parkinson’s, called the Whitehead team’s work “an important new step” in the development of the cell reprogramming technology. To generate cells suitable for transplanting into patients, several more steps are required, said Dr. Bjorklund, who works at Lund University in Sweden.

One is to develop a more precise recipe for generating the dopamine-producing neurons. There are several types, and the Whitehead team does not yet know how closely its cells resemble those of the substantia nigra, the brain region affected in Parkinson’s.

Another hurdle for attaining cells ready for transplant is to prove that all the cells are fully mature, since immature cells can produce tumors.

“We are easily talking about a few years” before achieving cells that could be considered for transplant, Dr. Bjorklund said.

 

Source Date: Mar 06 2009
Source Publication: New York Times
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