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Review
. 2022 May 21:14:11795735221092517.
doi: 10.1177/11795735221092517. eCollection 2022.

Current and Possible Future Therapeutic Options for Huntington's Disease

Mackenzie W Ferguson  1 , Connor J Kennedy  1 , Thulani H Palpagama  1 , Henry J Waldvogel  1 , Richard L M Faull  1 , Andrea Kwakowsky  1   2
Affiliations
Review

Current and Possible Future Therapeutic Options for Huntington's Disease

Mackenzie W Ferguson et al. J Cent Nerv Syst Dis. .

Abstract

Huntington's disease (HD) is an autosomal neurodegenerative disease that is characterized by an excessive number of CAG trinucleotide repeats within the huntingtin gene (HTT). HD patients can present with a variety of symptoms including chorea, behavioural and psychiatric abnormalities and cognitive decline. Each patient has a unique combination of symptoms, and although these can be managed using a range of medications and non-drug treatments there is currently no cure for the disease. Current therapies prescribed for HD can be categorized by the symptom they treat. These categories include chorea medication, antipsychotic medication, antidepressants, mood stabilizing medication as well as non-drug therapies. Fortunately, there are also many new HD therapeutics currently undergoing clinical trials that target the disease at its origin; lowering the levels of mutant huntingtin protein (mHTT). Currently, much attention is being directed to antisense oligonucleotide (ASO) therapies, which bind to pre-RNA or mRNA and can alter protein expression via RNA degradation, blocking translation or splice modulation. Other potential therapies in clinical development include RNA interference (RNAi) therapies, RNA targeting small molecule therapies, stem cell therapies, antibody therapies, non-RNA targeting small molecule therapies and neuroinflammation targeted therapies. Potential therapies in pre-clinical development include Zinc-Finger Protein (ZFP) therapies, transcription activator-like effector nuclease (TALEN) therapies and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas) therapies. This comprehensive review aims to discuss the efficacy of current HD treatments and explore the clinical trial progress of emerging potential HD therapeutics.

Keywords: Huntington’s disease; RNAi therapies; antidepressants; antipsychotic medication; antisense oligonucleotides; chorea; mood stabilizers.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Mechanisms of Huntington’s disease pathogenesis.
Figure 2.
Figure 2.
Tominersen and WVE-120101/WVE-120102 therapy development timeline.
Figure 3.
Figure 3.
Cellavita HD, foetal striatal stem CRT and autologous stromal/adipose-derived stem cell therapy development timeline.
Figure 4.
Figure 4.
ANX005 and VX15/2503 antibody therapy development timeline.
Figure 5.
Figure 5.
Non-RNA targeting small molecule (Pridopidine, Laquinimod, VX-745 and Nilotinib) therapy development timeline.
See this image and copyright information in PMC

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