An expert neurologist comments on the lack of an approved treatment for HD and examines the evolving treatment landscape, including interest in biomarkers.
This is a video synopsis/summary of a discussion involving Daniel Claassen, MD, MS.
In reflecting on the last 30 years of Huntington's disease (HD) research, there exists a collective frustration within the HD community due to the perceived lack of clear progress towards a treatment or cure. However, there is a recognition that significant strides have been made in exploring diverse approaches to address the complexities of HD. Notably, the concept of somatic expansion has gained prominence this year, shedding light on the instability of the CAG (cytosine, adenine, guanine) repeat as individuals age, particularly within the brain cells. This newfound understanding has sparked increased interest in therapies aimed at stabilizing this somatic instability, ranging from the development of new medications to exploring different DNA repair mechanisms.
A pivotal genetic discussion has emerged concerning biomarkers, with a focus on understanding disease burden and progression. While the mutant Huntington protein was initially optimistic as a potential biomarker, its utility has proven limited. In contrast, neurofilament light chain (NFL) has shown promise, particularly in blood samples, as a predictor of disease conversion or burden, especially in juvenile HD patients.
The transcript also delves into the evolution of staging criteria, introducing the ISS staging system. This system categorizes patients into stages zero to 3 based on the presence of MRI biomarker changes, clinical symptoms, and functional changes. The aim is to more accurately identify candidates for disease-modifying therapies by refining the understanding of disease progression.
Looking ahead, the transcript anticipates a greater emphasis on refining the new staging system, incorporating emerging biofluid biomarkers and clinical markers to enhance precision in identifying individuals suitable for disease-modifying therapies. Despite the frustration within the HD community, the transcript reflects a nuanced understanding of the current state of HD research, emphasizing the ongoing commitment to exploring diverse avenues in the pursuit of effective treatments.
Video synopsis in AI-generated and reviewed by NeurologyLive editorial staff.