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February 13, 2006 UMBI Medical Biotechnology Center Researcher Finds New Therapeutic Target for Huntington's Disease Baltimore, MD-In the February 6, 2006, advance access publication of Human Molecular Genetics, a group of UMBI scientists led by Dr. Mervyn Monteiro, reported that over expression of a novel regulatory protein, ubiquilin, can rescue and prevent Huntington’s disease symptoms in animal models. “This is an exciting report that we believe provides insight into a novel therapeutic target for Huntington’s disease,” said Dr. Jennie Hunter-Cevera, president of UMBI. “The scientific accomplishments of the talented faculty at UMBI’s Medical Biotechnology Center (MBC) continue to keep us at the forefront of discovery and meeting societal needs regarding human health.” Huntington’s disease (HD) is a devastating age-related neurological illness, affecting approximately, 1 in every 10,000 people in the US, and whose symptoms include severe behavioral and emotional disturbances and severe cognitive impairment. HD is a familial disease that is passed from parent to child through a mutation in the normal gene. Each child of an HD parent has a 50-50 chance of inheriting the HD gene. The disease is caused by an abnormal expansion of polyglutamine tracts in the gene encoding the huntingtin (htt) protein. The exact mechanism by which expanded polyglutamine tracts cause disease is not yet understood. However, proteins with longer polyglutamine repeats are more prone to aggregate, and it is believed that these aggregates may be toxic. Dr. Monteiro, an investigator at the MBC, discovered the protein ubiquilin while studying Alzheimer’s disease. Ubiquilin has been reported to bind to polyglutamine proteins. This prompted Dr. Monteiro to hypothesize that ubiquilin might be involved in regulating HD pathogenesis. In the current publication, Dr. Monteiro and his colleagues showed that when ubiquilin was over expressed in Caenorhabditis elegans (C. elegans) a type of worm that also serves as an animal model of HD, the worms no longer showed the motility defects associated with expression of toxic polyglutamine proteins. “Although a lowly worm, C. elegans share many traits with other animals, including man, and as such offer an important tool for investigating animal development,” said Bert Shapiro, Ph.D., of the National Institute of General Medical Sciences, which partially funded this work along with the National Institute on Aging. “Now Dr. Monteiro has used both this worm and cultured human cells to investigate how animals control the processes that can lead to nine different neurodegenerative disorders, most notably Huntington’s disease.” “Our finding is exciting because it raises the possibility that methods to modulate ubiquilin expression in humans may provide a novel therapeutic opportunity to treat Huntington's disease and other related polyglutamine disorders,” said Dr. Monteiro. To date, at least eight other neurological disorders are associated with an expansion of polyglutamine tracts; these disorders include dentatorubral-palidoluysian atrophy, spinal and bulbar muscular atrophy, and spinocerebella ataxias 1, 2, 3, 6, 7 and 17. Thus polyglutamine expansion causes several human neurological disorders, all of which may benefit from Dr. Monteiro’s research. ### Citation: Hongmin Wang, Precious J. Lim, Chaobo Yin, Matthias Rieckher, Bruce E. Vogel, and Mervyn J. Monteiro. Suppression of Polyglutamine-Induced Toxicity in Cell and Animal Models of Huntington's Disease by Ubiquilin. Human Molecular Genetics Advance Access published on February 6, 2006. doi:10.1093/hmg/ddl017 [Abstract] [Accepted Manuscript] ### Celebrating our 20th anniversary year, UMBI is Maryland's premier biotechnology research institute within the University System of Maryland and was established in 1985. The University of Maryland Biotechnology Institute (UMBI) consists of five major research and education centers and is dedicated to advancing the frontiers of biotechnology. UMBI’s centers of research include: CARB, the Center for Advanced Research in Biotechnology located in Rockville; CBR, the Center for Biosystems Research located in College Park; and COMB, the Center of Marine Biotechnology, MBC, the Medical Biotechnology Center, and IHV, the Institute of Human Virology, all located in Baltimore. For more information, visit www.umbi.umd.edu
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