title: Gene therapy in mouse models of huntington disease.
abstract: Huntingtin, the protein that when mutated causes Huntington disease (HD), has many known interactors and participates in diverse cellular functions. Mutant Htt (mHtt) engages in a variety of aberrant interactions that lead to pathological gain of toxic functions as well as loss of normal functions. The broad symptomatology of HD, including diminished voluntary motor control, cognitive decline, and psychiatric disturbances, reflects the multifaceted neuropathology. Although currently available therapies for HD focus on symptom management, the autosomal dominant cause and the adult onset make this disease an ideal candidate for genetic intervention. A variety of gene therapy approaches have been tested in mouse models of HD, ranging from those aimed at ameliorating downstream pathology or replacing lost neuronal populations to more upstream strategies to reduce mHtt levels. Here the authors review the results of these preclinical trials.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada. asouthwell@cmmt.ubc.ca
authors.forename: Amber L
authors.initials: AL
authors.lastname: Southwell
authors.forename: Paul H
authors.initials: PH
authors.lastname: Patterson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000150:complications / Q000235:genetics / Q000628:therapy; D001523:Mental Disorders / Q000209:etiology; D051379:Mice; D009069:Movement Disorders / Q000209:etiology; D009154:Mutation / Q000235:genetics; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation; D009687:Nuclear Proteins / Q000235:genetics; D034741:RNA, Small Interfering / Q000627:therapeutic use
chemical_list: C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D002118:Calcium