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 May 1, 2002 Glial Stem Cells Strengthen Ideas on How Cells Go Astray in ALS and Suggest How to Put Things Right Center Researcher Mahendra Rao uncovers stem cells' possibilities. Stem cell science is so new that Center researchers are testing perhaps several different types of the cells on their various animal models of ALS. Some of them are the very basic pluripotent stem cells that can give rise to almost every sort of tissue. Others are more restricted in what they can do, such as the multipotent stem cells capable, for example, of sparking every cell type in the nervous system. But, no matter what type of stem cell, the studies are clearing the murky waters of a new science and, in several cases, appear worthy of a better look for their therapeutic possibilities. The work of neurologist Mahendra Rao falls in that category. Rao's interests lie in one of the hottest areas of ALS research, focusing on nervous system cells called astrocytes. Center scientists have shown that astrocytes in ALS patients carry serious flaws that may contribute to the disease's advance. Specifically, patients' astrocytes fail to transport excess glutamate away from neighboring neurons. Glutamate is the excitatory chemical that tells motor neurons to fire. Too much of it, however, kills cells. Rao has, for years, studied how astrocytes develop in the body. Most recently, he teased their parent cells, a type of stem cell called a glial restricted precursor (GRP), from rat embryos and grew them in culture. Most important, Rao discovered that GRPs are rich in the transporter molecules astrocytes use to sop up glutamate. Could GRPs rescue tissue with dying motor neurons? Could they remove some of the glutamate that ailing astrocytes couldn't? The researchers suspected as much. As their model of choice, they used the Center's signature culture, a thin, living slice of rat spinal cord treated with a substance toxic to motor neurons. In collaboration with other Center researchers, GRPs were dropped on the cord, allowing the cells to engraft before adding the neurotoxin. A month later, the cultures with added stem cells displayed almost double the number of surviving motor neurons of those without-a clear protective effect. That effect suggests several therapeutic roads to follow. The obvious would be seeing if the same protective stem cell effect applies to people with ALS or other conditions, such as stroke, where excess glutamate causes harm. But stem cell therapy is a new, uncharted field, Rao says, and a more rapid approach might be one pharmaceutical companies are trying with other diseases, namely, try to make a drug that mimics or enhances the work of the glutamate transporters. It is, in essence, recreating the effect of the stem cells without their being there. "We have the transporter protein as an example to duplicate,"
says Rao, "and we have a system where you can test how it works."
Once the researchers make sure having more transporters is equally protective
for human cells, he adds, they'll investigate the drug approach. Would you like us to keep you informed of other news and updates in ALS
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