title: Emerging pharmacotherapies for neurodevelopmental disorders.
abstract: A growing and interdisciplinary translational neuroscience research effort for neurodevelopmental disorders (NDDs) is investigating the mechanisms of dysfunction and testing effective treatment strategies in animal models and, when possible, in the clinic. NDDs with a genetic basis have received particular attention. Transgenic animals that mimic genetic insults responsible for disease in man have provided insight about mechanisms of dysfunction, and, surprisingly, have shown that cognitive deficits can be addressed in adult animals. This review will present recent translational research based on animal models of genetic NDDs, as well as pharmacotherapeutic strategies under development to address deficits of brain function for Down syndrome, fragile X syndrome, Rett syndrome, neurofibromatosis-1, tuberous sclerosis, and autism. Although these disorders vary in underlying causes and clinical presentation, common pathways and mechanisms for dysfunction have been observed. These include abnormal gene dosage, imbalance among neurotransmitter systems, and deficits in the development, maintenance and plasticity of neuronal circuits. NDDs affect multiple brain systems and behaviors that may be amenable to drug therapies that target distinct deficits. A primary goal of translational research is to replace symptomatic and supportive drug therapies with pharmacotherapies based on a principled understanding of the causes of dysfunction. Based on this principle, several recently developed therapeutic strategies offer clear promise for clinical development in man.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University, Stanford, CA 94305-5485, USA.
authors.forename: Daniel Z
authors.initials: DZ
authors.lastname: Wetmore
authors.forename: Craig C
authors.initials: CC
authors.lastname: Garner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001321:Autistic Disorder / Q000188:drug therapy / Q000235:genetics; D001921:Brain / Q000002:abnormalities* / Q000187:drug effects / Q000503:physiopathology; D002648:Child; D003071:Cognition / Q000187:drug effects*; D002658:Developmental Disabilities / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000188:drug therapy / Q000235:genetics; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D009456:Neurofibromatosis 1 / Q000188:drug therapy / Q000235:genetics; D015518:Rett Syndrome / Q000188:drug therapy / Q000235:genetics; D014402:Tuberous Sclerosis / Q000188:drug therapy / Q000235:genetics
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