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The source of this study is the University of North Carolina: http://tinyurl.com/9nv3z University of North Carolina study may help explain the cause of a common, debilitating movement disorder By STUART SHUMWAY UNC School of Medicine CHAPEL HILL – Scientists at the University of North Carolina at Chapel Hill may have identified the genetic basis underlying essential tremor disease, the most common human movement disorder. The discovery comes from studies involving a strain of genetically altered mice that show the same types of tremor and a similar lack of coordination as people affected by essential tremor. This animal model of the disease might prove useful for screening potential treatments, according to the study team led by Dr. A. Leslie Morrow, associate director of the Bowles Center for Alcohol Studies and professor of psychiatry and pharmacology at UNC School of Medicine. “We believe that these mice could explain one etiology, or origin, of essential tremor disease in humans because of the marked similarities between the mouse model and the human disease,” said Morrow. “These mice are a fabulous model for screening new compounds for human essential tremor, and that’s probably the most exciting conclusion,” she added. A report of the findings will appear in the March issue of The Journal of Clinical Investigation. An estimated 5 million Americans are affected by essential tremor, a neurological disease that is characterized by an uncontrollable shaking of the limbs, in particular the arms and head. Unlike resting tremor associated with Parkinson’s disease, symptoms of essential tremor are noticeable during movement, such as lifting a cup of coffee. The causes of essential tremor disease remain unknown and current therapies are either partially effective or carry undesirable side effects. Morrow describes the finding as “serendipitous” because the study was initiated in an effort to learn more about alcoholism and the tremors that result from alcohol withdrawal. Her group had been examining a unique breed of laboratory mice that has been genetically engineered to lack a molecule called the gamma-aminobutyric acid-A (GABA-A) receptor alpha-1 subunit. GABA-A receptors reside on the surface of brain cells where they help the brain to relay “stop” messages throughout the body. Two alpha-1 subunits combine with three other proteins to form the most common type of GABA-A receptor, but this subunit is absolutely required for these GABA-A receptors to exist in brain. The mice lacking alpha-1 subunits have about 50% fewer GABA-A receptors in brain than normal mice. A defect in GABA-A receptor function could contribute to the loss of muscle control that characterizes essential tremor patients. “There is a reduction of the GABA-A receptor alpha-1 subunit in animal models of alcohol dependence,” noted Morrow, “so we wanted to study the mice. As soon as we obtained them we noticed that they had a tremor.” The symptoms in GABA-A receptor alpha-1 deficient mice had the same properties as those in people who suffer from essential tremor, suggesting to the authors that the mice might respond to drugs that are being used to treat human patients. “Very low doses of alcohol are effective at ameliorating tremor in human patients. Interestingly, we observed the same effect in these mice—they are exquisitely sensitive to alcohol,” observed Morrow. Additional compounds that ease the symptoms of essential tremor in humans, such as the anticonvulsant primidone and the beta blocker propranolol, also had partial alleviating effects in the mutant mice. “The work by the Morrow group clearly implicates the GABA system in human essential tremor,” remarked Kirk Wilhelmsen, associate professor of genetics and neurology at UNC. “These mice provide a framework for further pharmacologic study of essential tremor and currently are the best available model for the condition.” Future studies will examine essential tremor patients for polymorphisms or variations in the DNA sequence that might adversely affect GABA-A receptors. “This is one example of how animal research can lead to progress in understanding and treating human disease,” remarked Morrow. GABA-A receptor alpha-1 deficient mice were engineered and generated by collaborator Gregg E. Homanics of the University of Pittsburgh, a co-author in the study. In addition to Morrow, co-authors from the Bowles Center for Alcohol Studies include Dr. Jason E. Kralic, Dr. Hugh E. Criswell, Jessica Osterman, Todd K. O’Buckley, Mary-Beth E. Wilkie, and Dr. George R. Breese. Other co-authors include Dr. Douglas B. Matthews from the department of psychology at University of Memphis and Dr. Kristin Hamre from the department of anatomy and neurobiology at the University of Tennessee . The work was funded by grants from the National Institutes of Health, including the NIAAA. [ http://www.med.unc.edu/alcohol/faculty/MorrowAL/Morrow.htm ] ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn