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β-Blocker Use and Delayed Onset and Progression of Huntington Disease
Jordan L Schultz1,2,3, Amy C Ogilvie1, Lyndsay A Harshman4
1Department of Psychiatry, Carver College of Medicine at the University of Iowa, Iowa City.
Insights
Beta-blockers may offer a therapeutic benefit for Huntington disease (HD). This study found that beta-blocker use was associated with delayed motor symptom onset in premanifest HD and slower symptom progression in early motor-manifest HD.
Area of Science:
- Neurology
- Pharmacology
- Genetics
Background:
- Huntington disease (HD) is a neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric decline.
- Enhanced sympathetic tone is observed in HD, suggesting a potential therapeutic target.
Purpose of the Study:
- To investigate the impact of beta-blocker medication on the onset of motor symptoms and the progression of disease in individuals with Huntington disease.
- To evaluate the potential therapeutic role of beta-blockers in managing HD symptoms.
Main Methods:
- An observational, longitudinal, multicenter study utilizing the Enroll-HD database.
- Propensity score-matched cohorts of premanifest HD (preHD) and early motor-manifest HD (mmHD) patients were analyzed, comparing beta-blocker users (≥1 year use) with non-users.
- Outcomes included time to motor diagnosis for preHD and symptom progression rates (motor, functional, cognitive) for mmHD.
Main Results:
- In preHD patients, beta-blocker use was associated with a statistically significant reduction in the annualized hazard of receiving a motor diagnosis (HR, 0.66; P=.02).
- In mmHD patients, beta-blocker users exhibited slower annualized worsening in total motor score (MD, -0.45; q=.025), total functional capacity (MD, 0.10; q=.025), and symbol digit modalities test (MD, 0.33; q=.017) compared to non-users.
Conclusions:
- Beta-blocker use is associated with delayed motor symptom onset in premanifest Huntington disease.
- Beta-blockers may slow the progression of motor and functional decline in individuals with early motor-manifest Huntington disease.
- These findings suggest a potential therapeutic role for beta-blockers in Huntington disease management, warranting further investigation.
Importance:
Huntington disease (HD) is characterized by motor, cognitive, and psychiatric decline. β-Blockers may play a therapeutic role by decreasing enhanced sympathetic tone in HD.
Objective:
To evaluate the impact of β-blockers on the timing of motor diagnosis onset and progression of HD symptoms.
Design, Setting, And Participants:
This observational, longitudinal multicenter study used the Enroll-HD platform database (initiated September 2011 to present), including propensity score-matched cohorts of patients with premanifest HD (preHD) and early motor-manifest HD (mmHD) who were either users or nonusers of β-blockers. Participants included patients with genetically confirmed preHD (n = 4683 eligible participants) or mmHD (n = 3024 eligible participants) who were taking a β-blocker and were matched to similar non-β-blocker users.
Exposure:
Uninterrupted use of a β-blocker for more than 1 year.
Main Outcomes And Measures:
For PreHD: risk of receiving a motor diagnosis of HD over time. For mmHD: progression rate of total motor score, total functional capacity score, and the symbol digit modalities test. Post hoc analyses were performed to test additional clarifying hypotheses after the primary analyses were completed.
Results:
This study included 174 preHD β-blocker users (59 males; 115 females) with a mean age of 46.4 (SD, 13.1) years and a mean cytosine-adenine guanine repeat length of 41.1 (SD, 2.4) who were well matched to 174 preHD non-β-blocker users. The preHD β-blocker users showed a statistically significant reduction in the annualized hazard of receiving a motor diagnosis compared with nonusers (n = 174) (hazard ratio, 0.66; 95% CI, 0.46-0.94; P = .02). There were 149 mmHD β-blocker users (86 males; 60 females) with a mean age of 58.9 (SD, 11.3) years and a mean cytosine-adenine guanine repeat length of 42.0 (SD, 2.3) matched to 149 mmHD non-β-blocker users. The β-blocker users had a slower mean annualized worsening in total motor score (mean difference [MD], -0.45; 95% CI, -0.85 to -0.06; q = 0.025), total functional capacity score (MD, 0.10; 95% CI, 0.02-0.18; q = 0.025), and symbol digit modalities test (MD, 0.33; 95% CI, 0.10-0.56; q = 0.017) compared with matched nonusers.
Conclusions And Relevance:
In this study, β-blocker use was associated with delayed motor onset in preHD and reduced the rate of worsening of symptoms in mmHD. These findings demonstrated that β-blockers may have a therapeutic role in HD but further studies are required.
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