A research team from the University of Bergen in Norway, in collaboration with scientists at Harvard University in Cambridge, MA, examined the effect
Asthma drugs cut Parkinson’s risk, but seniors may have to think twice about taking beta-blockers for treating hypertension, as new research suggests that these drugs could double the risk of Parkinson’s disease.
The first author of the study is Shuchi Mittal, of Harvard Medical School, and the findings were published in the journal Science.
The research has several parts. First, the scientists conducted studies in cell cultures. Specifically, they searched for compounds that may downregulate the genetic expression of alpha-synuclein, which is the clumpy brain protein that builds up in excess and leads to Parkinson’s symptoms.
Using small molecule screening, the researchers found that a class of drugs called beta2-adrenoreceptor agonists has the potential to reduce alpha-synuclein expression.
Then, they tested these drugs in mice and stem cells. The preliminary results suggested that two kinds of beta2-adrenergic drugs may have opposing effects on the risk of Parkinson’s disease.
This prompted the team to further zoom in on these two types of beta2-adrenergic compounds: a beta2-adrenergic agonist called salbutamol (used for treating asthma), and beta2-adrenergic antagonists called beta-blockers (used for treating hypertension).
Asthma medication lowers risk by 34 percent
Mittal and colleagues looked at more than 100 million prescriptions registered in the Norwegian Prescription Database between 2004 and 2015.
Study co-author Prof. Trond Riise, of the Department of Global Public Health and Primary Care at the University of Bergen, says, “We analyzed the whole Norwegian population and found the same results as in the animal testing at Harvard University.”
Namely, that anti-asthma medication may significantly reduce the risk of Parkinson’s, while propranolol – a beta-blocker – may considerably increase it.
Patients who were taking salbutamol were 34 percent less likely to develop Parkinson’s, while those who took propranolol were twice as likely to develop the condition.
“These medicines have never been studied in relation to Parkinson’s disease,” says Prof. Riise. “Our discoveries may be the start of a totally new possible treatment for this serious disease. We expect that clinical studies will follow these discoveries,” he adds.
Significance of the findings
“It is important to note that association does not imply causation,” the authors caution. However, they suggest possible mechanisms that could account for the association found.
Beta-blockers, the researchers write, may “increase [alpha-synuclein gene] expression through H3K27 acetylation, resulting in alpha-synuclein accumulation, mitochondrial oxidative stress, dopaminergic neurodegeneration, and increased risk of PD [Parkinson’s disease].”
By contrast, the authors note, blood pressure medication may “promote dopamine neuron health by reducing [alpha-synuclein gene] expression (through H3K27 deacetylation) and mitochondrial free radicals.”
The authors say, “This may benefit nigral dopamine neurons,” which are predisposed to mitochondrial dysfunction in the early stages of Parkinson’s.
“Our study suggests a potential new pathway to target PD,” says corresponding author Dr. Clemens Scherzer, a neurologist and principal investigator at the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston, MA, and Harvard Medical School.
“Clinical trials will be needed to determine if these insights can be translated into patients with PD […] We are excited about this innovative drug development strategy. We hope it will speed up drug development for patients with PD and inspire therapeutic strategies for other brain diseases.”
Dr. Clemens Scherzer