Therapeutic advances in Huntington’s disease

ABSTRACT

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.

KEYWORDS:

• Huntington’s disease
• review
• clinical trials
• gene editing
• deep brain stimulation
• treatment
• tetrabenazine

Article highlights

• No disease-modifying treatments are currently available for Huntington’s disease (HD)

• Symptomatic treatment in HD is based mostly on expert-based recommendations.

• There is an increasing amount of agents that are seemingly efficacious in animal models of HD.

• More rigorous selection strategies and improved clinical study designs will empower the feasibility of a given agent to be proven efficacious in randomized clinical trials.

• Current biomarkers in HD are intended to be associated to a biologically relevant response to treatment, and predict clinically meaningful improvement.

• Ongoing clinical trials of potential therapies have a high likelihood of success when considering data from previous trials.

• Currently ongoing ‘gene editing’ therapies could become an unprecedented accomplishment in the treatment of autosomal dominant hereditary neurodegenerative diseases.

This box summarizes key points contained in the article.

Declaration of interest

JL López-Sendón has received travel grants from Krka pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.