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First step made toward curing ALS Add to ...

Ordinary skin cells taken from two elderly sisters afflicted with Lou Gehrig's disease have been transformed into nerve cells in a first step toward curing the fatal nerve disorder, U.S. researchers reported yesterday.

The advance, published in this week's edition of the journal Science, used a technique developed during the past two years that gives adult cells the same power as those from embryos to turn into any cell type in the body. The disease, also known as amyotrophic lateral sclerosis, or ALS, robs patients of muscular control and may eventually lead to paralysis.

The Harvard University team took a step toward fulfilling one of the promises of the new technology by creating lines of human stem cells from the tissue of patients with a genetic disease. The neurons created may, over time, show early signs of ALS, a disease that normally strikes people in their 50s and 60s, allowing researchers to study its workings and hunt for cures.

"We now have in the culture dish cells which have the same genetic makeup as do the patients," said Christopher Henderson, a researcher at Columbia University in New York and co-author of the study. "They are the very cells that are affected in the disease. This provides us the opportunity to study these motor neurons and see whether they behave in a manner that mimics the disease."

Nerve cells known as motor neurons were derived by the team using a method first developed by Shinya Yamanaka, a researcher at Kyoto University in Japan. It involves inserting four different genes into the skin cells, causing them to revert to a primordial state similar to embryonic stem cells.

The immediate potential of the method is that it will reveal the chemical and molecular changes that occur in motor neurons before they degenerate. It also will allow researchers to test a wide variety of chemical compounds on the cells to determine whether they can intervene in this process.

Because Dr. Yamanaka's method uses viruses to ferry the genes into the cells, it can trigger cancer and other undesired effects. Research teams around the world are now looking for alternative methods of reprogramming cells. Unless a safer method is found, the technique can't be used to make treatments.

Kevin Eggan, lead author of the study, said Dr. Yamanaka's technique provided a way to proceed with research that he and his colleagues had hoped to conduct by cloning patients' skin cells, the same method used in 1996 to create Dolly the sheep.

In that technique, the nucleus of a patient's skin cell is inserted into a human egg cell with its genetic material removed. Dr. Eggan said he and other scientists haven't obtained enough egg cells to successfully clone human cells because of ethical rules that bar researchers from paying egg donors for their time.

The Harvard Stem Cell Institute, where Dr. Eggan works, has spent about $100,000 (U.S.) on newspaper advertisements asking young women to donate their eggs for research. While the promotion generated hundreds of phone calls from interested women, only one provided an egg.

"When told they couldn't be compensated for their time, they rapidly lost interest," Dr. Eggan said. Women have to spend about 60 hours to provide eggs, partly to undergo uncomfortable and sometimes risky hormone treatments to stimulate the release of multiple eggs, Dr. Eggan said.

The new finding shows the skin cells of older patients can be used to make stem cells, even though researchers had been concerned that their age might prevent the process from working. The cells came from sisters who are 82 and 89 years old and are among the oldest living patients with ALS, according to the study.

Dr. Eggan said his team also is trying similar work using cells from patients with other forms of ALS.

 

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