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Investigation of Simvastatin Therapy in Smith-Lemli-Opitz Syndrome

State/Province Full: 
United States

Behavioral characteristics of autism, including irritability, social impairment, communication deficits and attention hyperactivity disorder, also occur in patients with mild forms of Smith-Lemli-Opitz syndrome (SLOS). This inherited disorder is caused by lack of an enzyme that converts 7-dehydrocholesterol (7-DHC) into cholesterol. When 7-DHC builds up after failing to convert to cholesterol, the build-up can be toxic. The drug simvastin impairs 7-DHC from being synthesized in the first place. It also may increase levels of the enzyme that can convert into cholesterol any 7-DHC that is produced. Can this drug, then, improve autism-like symptoms in patients with the mild form of SLOS? Can it provide clues to a potential role of cholesterol in autism spectrum disorders? One investigator's expertise in studying SLOS will be combined with the other investigator's expertise in conducting controlled clinical trials of simvastin. They will test the drug's efficacy in reducing autism-like behavioral symptoms, when given in conjunction with dietary cholesterol supplement, in 20 patients with mild SLOS who are between the ages of 4 and 18. They also will study whether simvastin, which can cross the blood-brain-barrier and enter the brain, increases cholesterol levels in the brain in a mouse model of SLOS, and in the human study participants. They hypothesize that symptomatic improvement will occur in response to increased levels of cholesterol in the brain, and that increased cholesterol will be associated with more normalized functioning of brain cells and neurotransmitters. Significance: The study will provide evidence of whether simvastin effectively reduces autism-like behavioral symptoms, as a potential treatment for children with autism spectrum disorders. The research also may reveal a potential role of cholesterol in these disorders.