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By KENDALL MORGAN Medical Center researchers have discovered a potential treatment for Huntington's disease. By enhancing the brain's natural protective response to the disease, researchers were able to alleviate the uncontrollable tremors and prolong the lives of mice with a neurological disorder that mimics Huntington's. Their finding suggests that a similar treatment strategy may be effective in humans. "This is exciting because it has implications for therapy," said Lawrence Steinman, MD, professor of neurological sciences and pediatrics and senior author of the study, published in the February issue of Nature Medicine. Huntington's disease is a hereditary disorder characterized by memory loss, abnormal movement and premature death. It affects 1 in 10,000 people, and children with an affected parent have a 50 percent chance of developing the disease. An abnormal form of the gene called huntingtin is at the root of the problem. In healthy people, the huntingtin gene encodes a protein with up to 34 glutamine molecules -- one of the essential building blocks of proteins -- at one end. When the number of these molecules on the protein exceeds 36, Huntington's disease results. But the normal gene function remains a mystery. Earlier research has indicated that the brains of Huntington's patients become clogged with clumps of protein called aggregates. These aggregates are formed when abnormal huntingtin proteins become hooked together. If the aggregates are the cause of the disease, Steinman reasoned, perhaps it could be controlled by preventing the two proteins from clumping into chains. He already knew that a compound called cystamine could keep the sticky protein under wraps. So, his former graduate student, Marcela Karpuj, PhD, now a postdoctoral fellow at University of California-San Francisco, began treating their sick mice with cystamine injections. The treated mice showed signs of improvement: the tremors and abnormal movements became less severe, and the lifespan of the mice increased 20 percent. But to the researcher's surprise, the protein aggregates remained unchanged. "The story, because it is science, took an unexpected turn," Steinman said. "We expected cystamine to inhibit the aggregations." Paper co-author Mark Becher, chief of neuropathology at the University of New Mexico Health Sciences Center, examined the brains of these mice, and found aggregations were the same after treatment. The researchers found that mice treated with cystamine had elevated expression of three particularly interesting genes -- all of which are known to encode proteins that play a protective role in the brain. These same proteins were found at increased levels in the brains of human Huntington's patients. The finding suggested that the brain in these patients makes an unsuccessful attempt to protect itself against the disease. Though the finding that cystamine could someday offer hope to patients with Huntington's disease is encouraging, the quest for other treatments will continue. "Before trying this with humans, we will search for ever more effective and specific compounds," Steinman said. "On the other hand, this is a horrendous, fatal disease. So we will have to see at what pace it will be applied to humans."
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Stanford, UCSF researchers home in on key gene in MS progression (11/28/01) |
Stanford Report, March 6, 2002
