Beta blockers delay age of onset and clinical symptom deterioration in Huntington disease: Study
A new study published in the Journal of American Medical Association showed that in motor-manifest Huntington disease (mmHD), Beta-blocker usage was linked to a slower rate of symptom deterioration and a delayed motor onset in preHD. An increased quantity of cytosine-adenine guanine (CAG) repeats in the HTT gene, which codes for the creation of the Huntingtin protein, is the cause of Huntington disorder (HD), a hereditary neurodegenerative illness.
The reduced parasympathetic and increased sympathetic tone are signs of autonomic nervous system dysfunction in HD patients. Cognitive, psychological, and motor deterioration are hallmarks of Huntington disease. By reducing HD's elevated sympathetic tone, β-Blockers could have a therapeutic effect. Thus, Jordan Schultz and colleagues carried out this investigation to assess how β-blockers affect the beginning of motor diagnosis and the development of HD symptoms.
Using the Enroll-HD platform database (launched in September 2011 to the present), this observational, longitudinal multicenter study included propensity score-matched cohorts of patients with premanifest HD (preHD) and early motor-manifest HD (mmHD) that were either β-blocker users or nonusers. The patients using β-blockers who had genetically proven preHD (n = 4683 eligible participants) or mmHD (n = 3024 eligible participants) and were matched to comparable non-β-blocker users were included in the study. The chance of eventually being given a motor diagnosis of HD is one of the primary outcomes and metrics for preHD in the case of mmHD, the pace at which the symbol digit modalities test, total motor score, and total functional capacity score progress. After the initial analyses were finished, post hoc analyses were carried out to evaluate more clarifying hypotheses.
The 174 preHD β-blocker users in this study were well matched to the 174 preHD non-β-blocker users, with a mean age of 46.4 years and a mean cytosine-adenine guanine repeat length of 41.1. The annualized risk of obtaining a motor diagnosis was statistically significantly lower for preHD β-blocker users than for nonusers. In comparison to 149 mmHD non-β-blocker users, 149 mmHD β-blocker users had a mean age of 58.9 years and a mean cytosine-adenine guanine repeat length of 42.0.
When compared to matched nonusers, the β-blocker users saw a slower mean annualized deterioration in the symbol digit modalities test, total motor score, and total functional capacity score. Overall, these findings showed that β-blocker medication in HD was linked to a later age of onset and a slower rate of clinical symptom deterioration by indicating that β-blockers may have therapeutic promise in HD.
Source:
Schultz, J. L., Ogilvie, A. C., Harshman, L. A., & Nopoulos, P. C. (2024). β-Blocker Use and Delayed Onset and Progression of Huntington Disease. In JAMA Neurology. American Medical Association (AMA). https://doi.org/10.1001/jamaneurol.2024.4108
