Jee Bang, MD, Johns Hopkins University School of Medicine, Baltimore, MD, discusses the clinical developments in establishing novel treatment methods for Huntington’s Disease (HD). In addition to antisense oligonucleotides (ASO), there are advances in RNA interference (RNAi) for gene-based therapy. This approach also causes mutant huntingtin mRNA degradation, using recombinant adeno-associated viral (AAV) vectors for microRNA delivery. An example of this gene therapy currently in clinical trials is AMT-130 (NCT04120493). Small molecules are another approach to HD therapy, with the efficacy of branaplam, an RNA splicing modulator, currently being investigated (VIBRANT-HD; NCT05111249). Other targets in clinical development include pridopidine (sigma 1 receptor agonist), ANX005 (monoclonal antibody targeting complement component 1q), and SAGE-718 (positive allosteric modulator of the NMDA receptor). Future approaches for HD therapy also include the potential need for combination therapy. This interview took place at the American Academy of Neurology 2022 Congress in Seattle, WA.