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By KRISTA CONGER The medical center announced Monday the creation of a multidisciplinary center devoted to Down syndrome research. The center will focus on the biological basis of Down syndrome and developing therapies to reverse or eliminate difficulties with cognition, speech, sleep and late-life decline in neurological function experienced by people with Down syndrome. The center’s mission, coupled with the scientific and clinical talent it has recruited, uniquely position it to understand and develop new treatments for the disorder. "There is real reason for hope," said William Mobley, MD, PhD, chair of neurology and neurosciences at the School of Medicine and director of the new center. "We may be able to help children with Down syndrome improve their ability to learn or, even better, prevent them from ever having symptoms." Preliminary results from Stanford researchers on a mouse model of Down syndrome suggest it may be possible to develop effective therapies for the disorder within the next few years. Because individuals with Down syndrome develop early-onset Alzheimer’s disease, the research also may benefit Alzheimer’s patients. In January, Mobley and his colleagues received a $2-million grant from the Hillblom Foundation to continue their research to study the neurobiology of Down syndrome. "Down syndrome is a serious problem that affects children," said Philip Pizzo, MD, dean of the medical school. "By better elucidating the biological mechanisms of Down syndrome we can develop new therapies and treatment modalities. We have a spectacular interdisciplinary neurosciences program to address these issues from a molecular- to a systems-level approach." More than 300,000 people in the United States have Down syndrome, which is caused by an extra copy of chromosome 21. Although it is the leading cause of mental retardation in the country, little research has been conducted at the molecular or neurological level to understand its symptoms or to explore potential therapies to help affected children and adults live more normal lives. Medical intervention has been primarily confined to supportive care tailored to deal with cognitive difficulties early in life, childhood heart disease and leukemia, and Alzheimer’s disease. "It used to be thought that once you were born with Down syndrome, it was too late to help," said Mobley, the John E. Cahill Family Professor at the medical school. "There are huge gaps in our understanding of how the extra chromosome causes such diverse clinical symptoms. We’re bringing scientists and clinicians together to fill those gaps and make a difference in these people’s lives." The Stanford-based center will operate under the auspices of the new Stanford Brain Research Center. It will consolidate the efforts of researchers and clinicians from the University of California-San Francisco, UC-Berkeley, UC-Irvine and UC-San Diego. The center’s scientists will use existing mouse models of Down syndrome to pinpoint the effect of the extra chromosome on gene expression, cell function, neuronal systems and, finally, clinical behavior. Their initial research efforts will target the problems with learning and memory that can prevent people with Down syndrome from leading independent lives; future research will focus on understanding and resolving problems with speech and language and sleeping difficulties. Preliminary research conducted by Mobley and Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences, suggests that abnormalities in nerve cell structure and signaling mechanism may be responsible for both the initial cognitive difficulties in Down syndrome children and the eventual neurological decline that afflicts affected adults. The scientists envision drug therapies that may enhance signaling capacity in the neurons of people with Down syndrome. Researchers are homing in on the specific genes on the human chromosome 21 that cause neurological trouble when present in three, rather than two, copies. Ongoing research in mice with smaller and smaller portions of the extra chromosome has considerably narrowed the list of possible perpetrators. Once the culprit is found, researchers will focus on reducing its expression, which may actually be easier than treating other diseases, such as cystic fibrosis and muscular dystrophy, caused by an absent or dysfunctional gene. "We’ll be trying to cut back on too much of a good thing," said Mobley, "instead of filling in something that’s missing entirely. All we have to do, theoretically, is find a drug that selectively reduces that gene’s expression by 33 percent, and we may have a therapy that can help people learn. "We can really understand this stuff," Mobley added. "The goal of the center is to apply our knowledge to the care of people in need."
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Experts assess future effects of age-related disease (3/21/01) |
Stanford Report, April 9, 2003
