Gene Therapy in Mouse Models of Huntington Disease
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.
Additional Information© 2011 The Author(s). The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: research from our laboratory that is cited here was funded by the National Institute of Neurological Disease and Stroke and the Hereditary Disease Foundation.
Accepted Version - nihms304300.pdf