Common heart medication shows therapeutic potential in Huntington disease

New research suggests that the use of beta-blockers may help delay the onset of motor symptoms in people with early-stage Huntington disease (HD), as well as reduce the worsening of symptoms in those already experiencing movement issues.

Among patients with premanifest HD, beta-blocker users had a 43-percent lower risk of receiving a motor diagnosis compared with nonusers (hazard ratio [HR], 0.66, 95 percent confidence interval [CI], 0.46–0.94; p=0.02). [JAMA Neurol 2024. doi:10.1001/jamaneurol.2024.4108]

Meanwhile, among patients with early motor-manifest HD, beta-blocker users had a significantly decreased mean annualized worsening in total motor score (mean difference [MD], −0.45, 95 percent CI, −0.85 to −0.06; q=0.025), total functional capacity score (MD, 0.10, 95 percent CI, 0.02–0.18; q=0.025), and symbol digit modalities test (MD, 0.33, 95 percent CI, 0.10–0.56; q=0.017) compared with nonusers.

In post hoc analyses, the investigators compared the effects of selective and nonselective beta-blockers on HD and examined whether the documented beneficial effect of the drugs on anxiety and other psychiatric symptoms in HD could have indirectly improved motor and functional symptoms. [Parkinsonism Relat Disord 2016;32:124-126]

The results indicated that users of selective and nonselective beta-blockers both showed clinical improvements compared with nonusers but not compared with one another. Additionally, anxiety scores did not significantly differ between beta-blocker users and nonusers, with the changes in anxiety scores having no correlation with the changes in motor, functional, and cognitive symptoms.

“Beta-blockers may exert their effects in HD by blocking norepinephrine signalling, although the exact mechanism remains unclear,” the investigators noted.

In an interview, lead study author Dr Jordan Schultz from the Carver College of Medicine at the University of Iowa in Iowa City, Iowa, US, emphasized that the present data represent early findings.

“We’re very much early on in the journey with beta-blockers and HD. There’s still a lot of work to be done to determine whether or not these [drugs] could be used as a potential treatment for patients with HD,” Schultz said.

“[What] I am most hopeful about is that these results provide some level of information that maybe we can modify the disease course. Maybe there are novel therapeutic targets that we can investigate further … [and] be able to identify better medications that would be a better therapeutic candidate for the next randomized controlled trial,” he added. “So, I think that these results open the door for new investigative directions in HD that could potentially lead to new trials for disease modifying therapies.”

For the study, Schultz and colleagues used data from the Enroll-HD platform database and established propensity score–matched cohorts of patients with premanifest HD and early motor-manifest HD. The premanifest cohort comprised 174 beta-blocker users (mean age 46.4 years, 66.1 percent female, 97.1 percent White) and 174 nonusers (mean age 48.1 years, 66.1 percent female, 96.6 percent White), whereas the motor-manifest cohort included 149 beta-blocker users (mean age 58.9 years, 42.3 percent female, 94.6 percent White) and 149 nonusers (mean age 59.4 years, 38.9 percent female, 94.6 percent White). Beta-blocker use was defined as uninterrupted use for more than 1 year.