Huntington's chorea: emerging fields in therapeutics (Review)

Neurogenetics. 2025 Sep 6;26(1):66. doi: 10.1007/s10048-025-00848-1.

Abstract

Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and psychiatric disturbances. It is caused by CAG repeat expansions in the HTT gene, resulting in the formation of mutant huntingtin protein that aggregates and disrupts neuronal function. This review outlines the pathogenesis of HD, including genetic, molecular, and environmental factors. Additionally, current management approaches and emerging therapeutic strategies-such as RNA interference, antisense oligonucleotides (ASOs), peptide inhibitors, and CRISPR/Cas9 gene editing-are discussed. Advancements in these novel therapies highlight a shift towards disease-modifying interventions. However, continued clinical and translational research is essential to develop a definitive cure.

Keywords: ASO; CAG repeat; CRISPR; Gene therapy; HTT gene; Huntington’s disease; RNAi.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Editing / methods
  • Genetic Therapy / methods
  • Humans
  • Huntingtin Protein / genetics
  • Huntington Disease* / genetics
  • Huntington Disease* / therapy
  • Oligonucleotides, Antisense / therapeutic use
  • RNA Interference
  • Trinucleotide Repeat Expansion

Substances

  • Huntingtin Protein
  • Oligonucleotides, Antisense
  • HTT protein, human