Therapeutic advances in Huntington's disease

Introduction: Huntington's disease (HD) is an autosomal dominant fully penetrant and fatal disorder caused by a CAG (glutamine) trinucleotide expansion in the huntingtin (htt) gene. To the date, there is no established disease-modifying treatment and the symptomatic therapies are limited. Recent advances in the understanding of HD pathology, natural history and improvements in clinical research methodology have provided an unprecedented opportunity to find effective treatments for HD.Areas covered: Current treatment options for motor, psychiatric and cognitive symptoms are discussed. Symptomatic therapies are, in most cases, limited to expert-based approaches rather than evidence-based medicine. Future therapeutic candidates include a wide spectrum of targets, including cellular energetic dysfunction, protein homeostasis, gene editing techniques and functional neurosurgery strategies. We review the spectrum of potential targets for future clinical research and the currently ongoing clinical trials in HD.Expert opinion: The likelihood of success based on previous data is high in some trials such as Pridopidine (Pride-HD), and encouraging in others, such as the new gene editing' strategies, which have already entered phase I human clinical trials and showed promising results from preclinical studies.