Heart medication may slow the progression of Huntington's disease

By Dr. Chinta SidharthanReviewed by Danielle Ellis, B.Sc.Dec 4 2024

Study finds β-blockers may delay onset and slow progression of Huntington's disease, offering potential as a therapeutic strategy

In a recent study published in JAMA Neurology, researchers investigated whether β-blockers, which regulate the sympathetic nervous system, affect the progression and onset of Huntington’s disease.

Using a large global dataset, the study evaluated the influence of β-blockers on delaying motor symptoms and slowing the progression of symptoms in individuals at various stages of Huntington’s disease.

Background

Emerging research has highlighted the involvement of autonomic nervous system dysfunction in Huntington’s disease. This is characterized by heightened sympathetic activity and reduced parasympathetic tone, which may contribute to disease pathology. This autonomic imbalance often manifests as elevated blood pressure and heart rate, possibly linked to early changes in central nervous system connectivity.

Medications such as β-blockers, which reduce sympathetic activity by antagonizing norepinephrine receptors, may address these dysfunctions. However, their role in altering the clinical course of Huntington’s disease remains unclear.

About the study

This longitudinal, observational study utilized the dataset from the Enroll-HD global research platform, which aggregates data from over 150 global research sites on Huntington’s disease. The researchers aimed to explore the potential influence of β-blockers on Huntington’s disease progression through analyses of cohorts of individuals in the pre-manifest (pre-Huntington’s disease) and early motor-manifest (mm-Huntington’s disease) stages.

The enrolled participants included adults above the age of 18 with genetically confirmed Huntington’s disease, meeting specific inclusion criteria to ensure homogeneity. For pre-Huntington’s disease, the eligibility criteria required a baseline diagnostic confidence level below 4, a CAG repeat length of 36 to 55, and a low motor score indicative of the pre-motor stage.

Those in the mm-Huntington’s disease group had a diagnostic confidence level of 4, mild functional impairment, and motor scores indicating early manifestation. Furthermore, all participants underwent matching procedures using propensity scores to ensure a balanced comparison between β-blocker users and non-users. Additionally, variables such as age, sex, genetic markers, and baseline health indicators were also considered during matching.

The participants who were classified as β-blocker users had consistently taken these medications for at least a year. The study excluded those who used β-blockers sporadically or initiated them during the study. Outcome measures for mm-Huntington’s disease included changes in motor, functional, and cognitive performance scores, while pre-Huntington’s disease analyses focused on the hazard of motor diagnosis.

Major findings

The study found that β-blocker use was associated with a delay in the onset of motor symptoms in individuals with pre-manifest Huntington’s disease and a reduction in symptom progression in those with early motor-manifest Huntington’s disease. These findings highlighted the potential therapeutic benefits of β-blockers in Huntington’s disease management.

In the pre-Huntington’s disease group, the β-blocker users exhibited a significantly reduced risk of receiving a motor diagnosis compared to non-users. The analysis revealed a hazard ratio of 0.66, indicating a 34% lower annualized risk of progression to motor manifestation for those on β-blockers. This delay suggested a modulatory effect of β-blockers on the disease onset.

For participants with mm-Huntington’s disease, the use of β-blockers was linked to slower rates of deterioration across several clinical measures. The participants who used β-blockers experienced a 0.45-point lower annualized decline in total motor scores compared to non-users. Similarly, functional capacity scores showed a slower annual decline, with a mean difference of 0.10 points favoring β-blocker users.

Additionally, cognitive performance, assessed through the symbol digit modalities test, also declined more gradually in the β-blocker group, with an improvement of 0.33 points compared to non-users. Notably, selective β-blockers demonstrated a more pronounced effect on slowing progression than non-selective ones, particularly in motor and cognitive domains.

Overall, the findings highlighted the potential of β-blockers in mitigating the impact of autonomic dysregulation in Huntington’s disease. However, the researchers believe that the variability in the effects across different β-blockers and their dosages indicates the need for further research to optimize therapeutic strategies.

Conclusions

To conclude, the study demonstrated that β-blockers are associated with delayed onset and slower progression of Huntington’s disease symptoms, which suggested a promising therapeutic role. By targeting the over-activity of the sympathetic nervous system, β-blockers may address key aspects of Huntington’s disease pathology.

However, the researchers stated that while these findings are significant, further research is needed to confirm causality, refine treatment protocols, and understand the mechanisms underlying these effects. Nonetheless, these findings pave the way for new interventions in Huntington’s disease management.