Therapeutic Strategies for Huntington's Disease: From the Bench to the Clinic

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG expansion in the HD gene that codifies the protein huntingtin. The disease is characterized by neurodegeneration of certain areas of the brain, particularly the striatum and the cortex. The first symptoms usually appear in mid-life and include cognitive deficits and motor disturbances that progress over time. The disease is invariable fatal and there is currently no cure for individuals affected with this disorder. HD transgenic mouse models have served as useful tools not only to elucidate the mechanisms underlying neurodegeneration in the HD brain, but also to test a number of therapeutic strategies for this disease. As a consequence of the promising results obtained in some of these preclinical studies, various pharmaceutical compounds have now been used in clinical trials. However, in most cases, the benefits observed in the clinical setting have been somewhat limited and, as such, the search for effective treatments still continues. In this review we present an overview of the various therapeutic strategies for HD that have received attention during the past decades, including the use of essential fatty acids, creatine, co-enzyme Q10, remacemide, riluzole, memantine, cystamine, minocycline, and tetrabenazine. We compare their efficacy in mitigating the neuropathology and symptoms of HD transgenic mouse models with the results that have been obtained with these compounds in clinical trials. Finally, we outline some recommendations that should be considered when designing future preclinical and clinical trials for the screening of potential therapeutic strategies for HD.