Daniel Claassen, MD, MS, reviews emerging treatment options for HD, and shares resources for patients, caregivers, and physicians to navigate diagnosis and management of HD.
This is a video synopsis/summary of a discussion involving Daniel Claassen, MD, MS.
In the landscape of Huntington's disease (HD) therapeutics, a predominant focus centers on mutant Huntington lowering therapies. These therapies aim to mitigate the impact of the expanded CAG (cytosine, adenine, guanine) repeat, which leads to the production of mutant Huntington protein. Several approaches have been explored, including antisense oligomer therapies, with Genentech and Roche's Generation HD study being a notable example. While this study did not meet its endpoint, ongoing efforts involve revising criteria and studying younger patients with minimal symptoms to explore the potential of antisense oligomers in altering the disease course.
Other allele-specific targets, such as those pursued by companies like Wave and VICO, focus on preserving the wild-type Huntington protein while targeting the mutant form. Though still in early development, these approaches hold promise in potentially benefiting patients. Additionally, oral medications employing RNA-splicing mechanisms have been investigated. While Branaplam faced setbacks due to adverse events like peripheral neuropathy, PTC Therapeutics continues development with a focus on reducing mutant Huntington protein levels.
Viral-mediated therapies, offered by companies like Unicure and Spark Therapeutics, present another avenue. These therapies involve AAV (adeno-associated virus) viral injections into specific brain regions, with the aim of permanently altering the production of mutant Huntington and wild-type Huntington proteins.
Beyond mutant Huntington lowering therapies, efforts have been made to alter HD progression through various mechanisms. Pridopidine, targeting the Sigma 1 receptor, faced challenges in meeting its endpoint, prompting further analysis to identify potential beneficiary subgroups. Ennexon's approach involves modifying the complement cascade to enhance synaptic function, with phase one results showing promise and plans for expansion.
Daniel Claassen, MD, MS, also emphasizes the importance of patient and clinician awareness, directing attention to resources such as the Huntington's Disease Society of America (HDSA) Center of Excellence program and the Huntington Study Group sites. Advocacy organizations, including HDSA and Huntington’s Disease Youth Organization (HDYO), provide valuable support and information. In the clinical realm, collaboration and involvement within the HD community are encouraged, recognizing the vast network of resources available for patients and families affected by this devastating disease.
Video synopsis in AI-generated and reviewed by NeurologyLive editorial staff.