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Ian Wilmut, the British scientist who helped clone Dolly the sheep, hopes to turn stem cells in a dish into motor neurons, the type of nerve cells ravaged in Lou Gehrig’s disease (also known as amyotrophic lateral sclerosis, or ALS). Creating a stem cell line with the disease would allow scientists to study how these neurons sicken and die and to search for ways to slow or stop the downward spiral of the disease. “I think that disease models, such as the ones we plan to create, will do more in the short term, and maybe the long term, to treat disease than cloning stem cells for tissue transplants,” Wilmut says.

One of the major advantages of cloned stem cells is that they would enable scientists to create accurate models of a disease without first determining the underlying genetics. “With a lot of sporadic diseases, we know there is a genetic component, but it’s not clear what it is or how it contributes to the development of the disease,” says Larry Goldstein, a neuroscientist at UCSD who studies Alzheimer’s disease. “We have a lot of hypotheses, and I think this methodology will put us in a position to test those hypotheses. And if one is correct, we’ll have a direction to go for therapy.”

A stem cell model of Alzheimer’s would also allow scientists to study what the disease does before symptoms appear and perhaps create early-diagnostic tests. By the time an Alzheimer’s patient goes to the doctor with cognitive problems, the brain is significantly – and possibly irreversibly – damaged. “Studying the brains of people who have already died is like studying a plane crash after the plane hit the ground – you’re looking at the wreckage,” says Goldstein. “We want to look at the black box of Alzheimer’s disease. What happens in those cells before the crash?”

To search for early signs of the disorder, scientists could generate stem cells using DNA from an Alzheimer’s patient, then prod the cells to differentiate into neurons, monitoring them for the production of specific proteins or other molecular changes not seen in neurons derived from healthy embryonic stem cells. The same approach might work with cancer, which is characterized by a series of harmful genetic changes. “We want to know what’s the earliest you can detect differences in disease cells,” says Renee A. Reijo Pera, codirector of UCSF’s human-embryonic-stem-cell biology program.

Cloned stem cells may also provide a much more effective way to test drugs. “Very often the animal models that exist for a particular disease really don’t authentically replicate what’s going on in a human,” says Snyder. Using models based on stem cells, scientists could test drugs at different stages of disease, searching for compounds that could prevent a person at risk for, say, Alzheimer’s, from ever developing the disease in the first place, or for compounds that stop or reverse the progression of damage in people who already have the disease.

Snyder eventually hopes to create stem cell models of many different neurodegenerative diseases. His first step, in collaboration with Friedmann, will be to use the frozen skin cells housed at UCSD to create stem cells with Lesch-Nyhan disease. Snyder originally hoped Hwang would teach him the cloning process. But now the scientists plan to embark on the therapeutic-cloning project on their own and are working on getting regulatory approval and state or private funding.

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