Huntington's disease (HD) is an autosomal, progressive, dominant inherited neurological disorder characterized by motor dysfunction, cognitive decline, and psychiatric symptoms. HD is caused by abnormal expansion of trinucleotide CAG in exon1 of the Huntington gene and the accumulation of mutant huntingtin (mHTT) fragments, which leads to neurotoxicity mainly in the brain's cortex region. This review aimed to collect current research on developing effective treatment strategies, including small-molecule approaches, gene therapies, and protein degradation techniques to reduce the mHTT levels. We further discuss various therapeutic strategies, including CRISPR-based approaches and small-molecule targeted protein degradation. Additionally, the potential of VTX-003 and ANX005 in mitigating disease progression is explored. Despite these promising therapies, challenges persist, particularly in long-term assessment, delivery strategy, and off-target effects. Considering the future landscape and need, the review has strengthened the need of therapeutic interventions to enhance efficacy and safety, ultimately improving the quality of life of HD patients.
Gulzar et al. (Thu,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: