Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG expansion in the HD gene. The disease is characterized by neurodegeneration, particularly in the striatum and cortex. The first symptoms usually appear in mid-life and include cognitive deficits and motor disturbances that progress over time. Despite being a genetic disorder with a known cause, several mechanisms are thought to contribute to neurodegeneration in HD, and numerous pre-clinical and clinical studies have been conducted and are currently underway to test the efficacy of therapeutic approaches targeting some of these mechanisms with varying degrees of success. Although current clinical trials may lead to the identification or refinement of treatments that are likely to improve the quality of life of those living with HD, major efforts continue to be invested at the pre-clinical level, with numerous studies testing novel approaches that show promise as disease-modifying strategies. This review offers a detailed overview of the currently approved treatment options for HD and the clinical trials for this neurodegenerative disorder that are underway and concludes by discussing potential disease-modifying treatments that have shown promise in pre-clinical studies, including increasing neurotropic support, modulating autophagy, epigenetic and genetic manipulations, and the use of nanocarriers and stem cells.
Keywords: Huntington’s disease; autophagy; clinical trial; disease-modifying treatment; epigenetics; genetics; pre-clinical study; transgenic mouse model; trophic support.