Huntington’s disease (HD) is a hereditary neurodegenerative pathology that affects around 4,000 people in Spain, according to the Spanish Federation of Rare Diseases (FEDER). Unfortunately, there is no cure, so treatments are intended to relieve symptoms and improve patients’ quality of life. Now, the discovery of a group of researchers from the University of Iowa Health Care (UI) could be a ray of hope for those affected and their loved ones, since they have proven that a drug used to treat heart problems can delay the progression of Huntington’s.
The team of scientists analyzed clinical data recorded in a large observational database of more than 21,000 people with Huntington’s and found that the use of beta-blocker drugs (commonly used to treat heart and blood pressure conditions) was associated with both a significantly later onset of disease symptoms in people in the presymptomatic stages, as well as a slower rate of worsening of symptoms in patients with symptoms.
“Given that there are no HD-modifying agents for Huntington’s disease, the possibility that beta-blockers, which are inexpensive and have a known safety profile, could provide benefit to patients at various stages of the disease is very exciting,” he said. in a note published by UI Jordan Schultz, assistant professor of psychiatry at the aforementioned university and lead author of the study, which was just published in JAMA Neurology.
Delay or prevent the onset of Huntington’s symptoms
The mechanism of action of beta blockers is to block the action of norepinephrine, a neurotransmitter and hormone that intervenes in the “fight or flight” response. Schultz and his colleagues focused on these drugs because their previous research had shown that, compared to healthy people, HD patients appear to have a stronger “fight or flight” reflex, even when at rest.
“Patients with Huntington’s disease have a slightly more active sympathetic nervous system, which is what drives the fight-or-flight response, and theoretically they have more norepinephrine,” explains Schultz. “We hypothesized that this subtle change may contribute to the neurodegeneration that occurs in HD, and since beta-blockers inhibit the action of norepinephrine, we wanted to know if they could have a therapeutic role in HD patients.”
To investigate the possible effect of beta-blocker use, the UI researcher used data from the world’s largest observational study for families with Huntington’s disease, known as Enroll-HD. This database follows more than 21,000 patients diagnosed with HD or at risk for the disease throughout their lives, and collects annual clinical information on motor, functional and cognitive symptoms, as well as medication use.
UI researchers identified two distinct groups of HD patients: those with the genetic mutation that causes the disease, but who have not yet begun to show significant clinical symptoms (pre-HD group), and patients who have already received a diagnosis clinical HD, called patients with motor manifestation (mmHD group). Within each group, they identified patients who had been taking a beta blocker for at least one year.
“These results provide early evidence that the autonomic nervous system may be a therapeutic target for the modification of Huntington’s disease.”
Next, the team matched 174 preHD and 149 mmHD beta-blocker users with the same number of similar users who did not use beta-blockers. The team’s analysis showed that pre-HD beta-blocker users had a significantly lower annual risk of receiving a clinical diagnosis of HD compared to non-beta-blocker users, indicating that beta-blocker use was associated with later onset. of HD.
Among the mmHD group, the researchers demonstrated that patients taking beta-blockers had a notable slowing of the gradual worsening of motor, cognitive, and functional symptoms compared to non-users. Delaying or preventing the appearance of HD symptoms is a primary objective to modify the course of the disease. By demonstrating that beta-blockers were associated with a slowing of disease progression in both the presymptomatic and symptomatic phases, these new results suggest that beta-blockers may be beneficial for patients at various stages of the disease.
“Importantly, this study reports associations between beta-blocker use in HD patients and delaying the onset and slowing disease progression, but the data do not prove cause and effect,” cautions Schultz, who is also a member from the Iowa Neuroscience Institute. “However, these results provide early evidence that the autonomic nervous system may be a therapeutic target for the modification of Huntington’s disease.”
In addition to conducting further research to understand how the autonomic dysfunction seen in HD could be targeted for disease modification, the UI team also hopes to conduct a clinical trial of beta-blockers as a potential Huntington’s disease modifier.
