BEGIN:VCALENDAR VERSION:2.0 X-WR-CALNAME:News PRODID:-//Sitemason, Inc//Sitemason Calendar//EN CALSCALE:GREGORIAN METHOD:PUBLISH BEGIN:VEVENT UID:http://sitemason.vanderbilt.edu/element/9ty79cs/id/56791 SUMMARY:$4.5 Million Drug Discovery Grant Awarded to Vanderbilt University Medical Center DESCRIPTION:Vanderbilt University Medical Center has received a $4.5 million grant from Seaside Therapeutics to find potential treatments for fragile X syndrome\, the most common inherited form of mental retardation and the most common genetic cause of autism. \;\n\n\n\n&ldquo\;It&rsquo\;s a really innovative idea\,&rdquo\; said Jeffrey Conn.\, Ph.D.\, director of the Vanderbilt Program in Drug Discovery and principal investigator of the fragile X project. &ldquo\;If it works\, it could be transformative &hellip\; it could totally change the way people view developmental disorders.&rdquo\;\n\n\n\nResearch conducted by founders of Seaside Therapeutics and others indicates that excessive signaling through a particular receptor in the brain called mGluR5 may be responsible for the neurological and psychiatric consequences of fragile X syndrome.\n\n\n\nSelective inhibition of the receptor potentially could reduce or eliminate these devastating effects\, company officials said.\n\n\n\nUsing Vanderbilt&rsquo\;s high-throughput screening facility\, which is capable of testing tens of thousands of small molecules for drug-like activity in a single day\, Conn and his colleagues have identified more than 400 novel compounds that inhibit mGluR5.\n\n\n\nSupported by the three-year Seaside Therapeutics grant\, the Vanderbilt researchers will use medicinal chemistry\, molecular biology\, pharmacology and efficacy studies to develop compounds with the drug-like properties required for further study in fragile X. \;\n\n\n\n&ldquo\;We&rsquo\;re at a very early stage\,&rdquo\; said Conn\, a professor of Pharmacology who serves on the scientific advisory board of Seaside Therapeutics. &ldquo\;It now becomes a really high-level molecular engineering effort.&rdquo\;\n\n\n\nSeaside Therapeutics will contribute scientific and drug-development expertise\, and will select compounds from the collaboration to carry forward into clinical development.\n\n\n\n&ldquo\;Importantly\, the Vanderbilt team shares Seaside&rsquo\;s passion for helping children with fragile X -- creating a strong partnership focused on rapidly translating new discoveries in neurobiology into desperately needed novel treatments\,&rdquo\; said Randall Carpenter\, M.D.\, co-founder\, president and CEO of the Cambridge\, Mass.-based firm.\n \;\n \;\nAbout Fragile X syndrome\: \;\n\n\n\nFragile X syndrome is relatively rare\, affecting approximately 90\,000 people in the United States. It is caused by a mutation in the FMR1 gene on the X chromosome that prevents expression of a single protein\, the fragile X mental retardation protein (FMRP). \;\n\n\n\nThe absence of FMRP gives rise to the major symptoms of fragile X syndrome in humans -- impaired cognitive function\, developmental delay\, attention deficit and hyperactivity\, anxiety\, obsessive-compulsive and autistic behaviors.\n\n\n\nA key advance was the isolation of the FMR1 gene and subsequent generation of the Fmr1 knockout mouse &ndash\; an animal model that lacks FMRP and mimics the human condition. \;\n\n\n\nBy studying the brains of these mice\, Seaside scientific founder Mark Bear\, Ph.D.\, \;Picower Professor of Neuroscience at MIT\, discovered a connection between metabotropic glutamate receptor subtype 5 (mGluR5) signaling and fragile X syndrome. \;\n\n\n\nStudies by Bear and others indicate that excessive signaling through mGluR5 may be responsible for the consequences of fragile X syndrome.\n \;\nAbout Seaside Therapeutics\:\nSeaside Therapeutics is creating new drug treatments to correct or improve the course of fragile X syndrome\, autism and other disorders of brain development. We are dedicated to translating breakthrough discoveries in genetics and neurobiology into therapeutics that improve the lives of patients and their families. \n \;\nAbout the Vanderbilt Drug Discovery Program\:\n\n\n\nVanderbilt scientists led by Jeffrey Conn\, Ph.D.\, have pioneered the discovery of &ldquo\;allosteric&rdquo\; compounds that modulate (&ldquo\;turn up&rdquo\; or &ldquo\;turn down&rdquo\;) the activation of certain receptors\, called metabotropic glutamate receptors\, when the neurotransmitter glutamate binds to them.\n\n\n\nConn&rsquo\;s colleagues in this effort include Craig Lindsley\, Ph.D.\, director of Medicinal Chemistry in the drug discovery program\, who will oversee chemical optimization of compounds for testing in the clinic. \;\n\n\n\nLindsley helped discover the first &ldquo\;positive&rdquo\; modulators of mGluR5\, which &ldquo\;turn up&rdquo\; the receptor&rsquo\;s activation when it binds to glutamate.\n\n\n\nDavid Weaver\, Ph.D.\, directs the high-throughput screening facility in the Vanderbilt Institute of Chemical Biology\, which is capable of testing tens of thousands of small molecules for drug-like activity in a single day.\n\n\n\nHe and Alice Rodriguez\, Ph.D.\, a research instructor in Pharmacology\, will lead the search for &ldquo\;negative modulators&rdquo\; that can &ldquo\;dim&rdquo\; the mGluR5 &ldquo\;switch\,&rdquo\; and they will oversee molecular pharmacology efforts required to screen lead compounds in cell-based assays. \;\n\n\n\nCarrie Jones\, Ph.D.\, research assistant professor of Pharmacology and director of Behavioral Pharmacology for the drug discovery program\, will spearhead the screening of lead compounds in rodent behavior models. URL;VALUE=URI: CATEGORIES:medical-center CLASS:PUBLIC SEQUENCE:1 DTSTAMP:20081122T032719 CREATED:20080613T092713 LAST-MODIFIED:20080613T092713 DTSTART:20080204T092000 END:VEVENT END:VCALENDAR