In an unexpected finding, researchers demonstrated that certain asthma drugs might protect from developing Parkinson’s disease by lowering the production of the disease-linked protein alpha-synuclein.
But researchers caution against attempting to medicate with such drugs before clinical trials establish they are safe in this patient group, and that they really have an impact on the processes of Parkinson’s disease.
The findings, published in the journal Science are only the very first step in a process that might lead to new treatments, the research team from Harvard Medical School and Brigham and Women’s Hospital in Boston said.
“We think this is an exciting potential pathway to developing new treatments for Parkinson’s,” Clemens Scherzer, MD, said in a press release. Scherzer is a neurologist and senior study author.
The team’s discovery, described in the report “β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease,” was based on the assumption that it might be possible to treat Parkinson’s by lowering the production of alpha-synuclein in the brain.
Alpha-synuclein is the main component of protein aggregates — Lewy bodies — in Parkinson’s patients’ brains. But with the exception of certain rare inherited cases in which people have mutated forms of the protein, researchers are not sure if the aggregates really are a disease cause. They also might appear as a result of disease processes.
But research teams around the world already have started developing drugs that clear alpha synuclein from the brain or target it in other ways.
The Boston-based team, instead, figured there might already be approved drugs that act to minimize the production of the protein. Screening more than 1,100 compounds, they found that drugs that boost the activity of the beta-2 adrenergic receptor were most potently doing just that.
They tested their idea on mice exposed to a chemical that triggers Parkinson’s-like neurodegeneration. Animals exposed to the beta-2 boosting drug clenbuterol alongside the toxic chemical had much less neurodegeneration in the substantia nigra — the brain area holding a majority of dopamine-producing cells that die in Parkinson’s.
They also turned to a database of more than 4 million people followed more than 11 years. Just as they suspected, they noted that among more than 600,000 people who had used a beta-2 targeting drug for asthma, a Parkinson’s disease diagnosis was one-third less likely.
But the impact of drugs targeting the beta-2 receptor goes both ways. In contrast to asthma drugs, in which the beta-2 receptor is activated, certain heart and blood pressure medications block the receptor.
The team noted that people using drugs that blocked beta-2 receptors had a doubled risk of developing Parkinson’s compared to people who never used such drugs. In lab studies, they could confirm that blocking beta-2 boosted the production of alpha-synuclein.
But researchers stressed that the study does not prove that asthma drugs prevent Parkinson’s, or that heart medications cause it.
“You need a clinical trial to prove cause-and-effect,” said Scherzer. But he also underscored that rather than testing current asthma drugs, it would be wiser to improve current beta-2 activators and tailor them for the specific task of decreasing alpha synuclein.
It also might be a good idea to target patients with genetic flaws in the alpha-synuclein gene that are confirmed to put people at risk of the disease, as the effect of such drugs might be contingent on a person’s genetic makeup.
In the short run, researchers were, however, more concerned about the implication of their identified link between beta-blocking heart medications and Parkinson’s disease. While they stressed that patients should not quit any drugs that they need for blood pressure control of heart disease, concerned patients might check with their doctors about other types of drugs that might work for them.
This idea also was endorsed by Evan Snyder, MD, PhD, a professor at Sanford Burnham Prebys Medical discovery Institute in San Diego, and the author of an accompanying perspective piece in Science.
Snyder also approached the issue of the potentially uncontrolled use of asthma medications to treat Parkinson’s. Physicians have the right to prescribe medications off-label, meaning they are given for a condition other than the approved ones.
“The big caution here is that these are FDA-approved medications, and doctors could prescribe them off-label. My worry is that people might take these drugs in an unregulated fashion,” said Snyder.
But, just as the research team did, he found the results promising.
“I think this is enough to justify moving toward properly done clinical trials,” said Snyder .