Heart medication may slow Huntington’s disease progression
Trial data show beta-blockers may be targets for modifying disease course
Beta-blockers, a class of medicines often used to manage heart and blood pressure issues, may slow the onset and progression of Huntington’s disease, according to data from Enroll-HD, the world’s largest observational study in Huntington’s.
“Given that there are no disease-modifying agents for HD [Huntington’s disease], the possibility that beta-blockers, which are cheap and have a known safety profile, may provide benefit to patients at various stages of the disease is very exciting,” Jordan Schultz, the study’s first author and an assistant professor of psychiatry at the University of Iowa, said in a university news story. “While these represent early results, they provide hope that there may be novel targets … for modifying the disease course of HD.”
The study, “[Beta-Blocker] Use and Delayed Onset and Progression of Huntington Disease,” was published in JAMA Neurology.
Huntington’s is a neurodegenerative, genetic disease marked by symptoms including movement deficits, cognitive impairment, and psychiatric changes. Increasing research shows that Huntington’s patients also have abnormalities in the autonomic nervous system, which controls involuntary bodily functions like breathing, digestion, and heart rate.
Autonomic dysfunction symptoms, including higher heart rate and blood pressure, have been reported in people carrying a Huntington’s-causing mutation about two decades before the predicted onset of motor symptoms. Recent data have suggested that Huntington’s patients have overactivity of the part of the autonomic nervous system that governs fight-or-flight responses, which is called the sympathetic nervous system.
Analyzing the data
Nerve cells in the sympathetic nervous system communicate with the rest of the body by releasing a signaling molecule called norepinephrine. Beta-blockers, which block the activity of this signaling molecule, are commonly used to help lower heart rate and blood pressure.
While these medications “may uniquely block an overactive sympathetic nervous system in patients with HD,” the researchers wrote, “it is unclear if the use of [beta-blockers] is associated with an altered disease course in patients with HD.”
“Patients with HD have a slightly more active sympathetic nervous system … and theoretically have more norepinephrine,” Schultz said. “We have hypothesized that this subtle change may be contributing to the neurodegeneration that occurs in HD, and because beta-blockers inhibit the action of norepinephrine, we wanted to know if they might have a therapeutic role in patients with HD.”
To test this idea, the scientists analyzed data from Enroll-HD, a global study collecting demographic, clinical, and medication information from more than 21,000 people either diagnosed with Huntington’s or at risk for the disease.
In a first analysis, the researchers looked at people carrying a Huntington’s-causing mutation who did not yet have any motor symptoms that would be needed to confirm a Huntington’s diagnosis (referred to as premanifest Huntington’s).
Of 4,683 of those people, 174 were taking beta-blockers. These were matched in terms of demographic and clinical factors to an equal number of patients who were not on these medications.
Results showed that premanifest Huntington’s patients taking beta-blockers were significantly less likely to progress to full-blown disease, by about 43%, relative to non-beta blocker users. This suggested that use of beta-blockers was linked to a later Huntington’s onset.
Motor symptoms
The team then focused on the 3,024 eligible participants with early motor-manifest Huntington’s. They compared rates of disease progression between 149 of these patients who were on beta-blockers and a matched group of 149 nonusers.
Data demonstrated that motor symptom severity scores worsened significantly more slowly in beta-blocker users. Early-stage Huntington’s patients on beta-blockers also had slower worsening in measures of functional ability and cognition.
“We have demonstrated that the use of [beta-blockers] was associated with a significantly lower annualized risk of receiving a clinical diagnosis of HD in participants with [premanifest Huntington’s],” the researchers wrote. “Furthermore, [beta-blockers] were associated with a slower rate of worsening of clinical symptoms of HD among participants with [early motor-manifest Huntington’s].”
While it’s possible that beta-blockers’ ability to reduce activity of the fight-or-flight part of the nervous system may lessen anxiety could make patients appear to have better function even when the underlying disease is not being affected, there were no notable differences in anxiety scores between patients who were or weren’t on beta-blockers. The researchers said this suggests these medications may actually have an impact on Huntington’s disease, though they stressed that further studies are needed to prove this idea.
“It is important to note that this study reports associations between beta-blocker use in patients with HD and delayed onset and slowing of disease progression, but the data does not prove cause and effect,” Schultz said. “However, these results provide early evidence that the autonomic nervous system may be a therapeutic target for disease modification of HD.”
The team hopes to conduct a clinical trial to test the effects of beta-blockers in Huntington’s patients, the university said.
About the Author
