Asthma and high blood pressure drugs influence risk of developing parkinson’s disease.

Outwardly, Parkinson’s disease (PD) appears as tremors and stiffness. In the brain, neurons fill with aggregates of α-synuclein protein. Reducing α-synuclein decreases symptoms. An international team, using data on 4.6 million Norwegians over 11 years, now report in Science that two common types of drugs alter α-synuclein production. These drugs, for asthma and high blood pressure, may influence risk of PD. Norwegian researchers on the study were from University of Bergen, Haukeland University Hospital, and Norwegian Institute of Public Health.

Professor Trond Riise, Department of Global Public Health and Primary Care, University of Bergen, was asked to lead analysis of the Norwegian data because of a visiting professorship at Harvard University, where the work began. “We have an advantage in the Nordic countries,” he says. “With our databases and health registries we have the power to study large populations.”

Riise’s collaborators started by screening 1 126 different drugs and supplements. They found that drugs that act on the ß2-adrenoreceptor (ß2AR) cause marked changes in α-synuclein levels in cultured neural cells. Tests in mice confirmed that ß2AR agonists, which stimulate the receptor, reduce α-synuclein, and antagonists, which block ß2AR, increase the protein. ß2AR and similar receptors affect diverse organs, including the heart and vascular systems. Chronic asthma may be treated with ß2AR agonists; hypertension may be treated with antagonists.

Effects in humans

Determining the real-world effects of ß2AR-targeting drugs on PD was up to Riise’s research group. “We tested if the in vitro and animal model results held in a general human population,” he says. The scientists analyzed data from health records and the Norwegian Prescription Database.

The results strongly supported a link between PD and ß2AR-acting drugs. Compared to the general population, people taking a ß2AR antagonist for hypertension had a two-fold increased PD risk. (Patients taking these nonspecific ß blocker drugs can talk with their doctors about their medications.) People taking ß2AR agonist drugs for chronic asthma had less PD risk.

The effect was dose dependent, with the highest dose showing the greatest effect – 55% reduced risk.

Riise says we don’t know if the drugs affect existing PD, but the clinical and pharma worlds are considering treatment implications, drug modifications, and trials based on the results. He and his collaborators might apply the same in vitro, in vivo, and population epidemiology approach to finding drugs that alter other risks, such as for Alzheimer’s disease.

“It’s a new way of attacking disease,” he says. “Not looking at damage that has occurred, but going upstream to stop the disease process before it happens.”