Overview of Huntington's Disease and Emerging Treatment Strategies: A Narrative Review

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by a cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (HTT) gene. The symptoms of HD include severe motor dysfunction, cognitive issues, and emotional dysregulation. These combined issues are not only debilitating but also lead to depression/anxiety, increased suicide rates, and caregiver burnout. Our narrative review summarizes several recent studies examining the efficacy and differences among emerging treatment strategies for HD. A systematic search of peer-reviewed literature was conducted, focusing on recent studies that describe molecular genetic manipulation of the HTT gene/huntingtin protein. The results of our narrative review reveal potential benefits in slowing disease progression and enhancing symptomatic management through genetic silencing, gene editing using Clustered Regularly Interspaced Short Palindromic Repeats technology, antisense oligonucleotide-mediated protein suppression, RNA interference, sirtuin modulation, and ferroptosis inhibition. Future studies should aim to examine the disease progression of HD models using multimodal therapeutic options with efficient delivery methods to deep brain structures, as well as to develop biomarkers to track disease progression and treatment response.