A robust Norwegian analysis found that the use of asthma medicine halves the risk of getting Parkinson’s disease, while one type of medicine against high blood pressure doubles the risk.
Researchers at the department of global public health and primary care (IGS) at the University of Bergen (UiB) have completed a large study that included data from the Norwegian Prescription Database, in cooperation with researchers at Harvard University. “Our analysis of data from the whole Norwegian population has been decisive for the conclusion in this study,” says Professor Trond Riise at IGS. He leads the registry study in Norway.
Together with colleagues Anders Engeland and Kjetil Bjørnevik, Riise has analysed more than 100m Norwegian prescriptions registered since 2004. In the study, the treatment of Parkinson’s was linked to prescriptions of asthma medicine and the medicine for high blood pressure. It enabled the researchers to see the connection between medicine use and illness.
The UiB-researchers were able to make these comparisons by using the prescription database. The Norwegian analysis was done after researchers at Harvard University found these effects of the medicines in animal tests and in experiments with brain cells in the lab. Their results showed that these different medicines had opposite effects on the risk of Parkinson’s.
To find out if these medicines had the same effect on humans, the researchers at Harvard University started to collaborate with the Norwegian research team, and their unique resource of having access to the unique and large Norwegian database, where all Norwegian prescriptions are registered.
“We analysed the whole Norwegian population and found the same results as in the animal testing at Harvard University. These medicines have never been studied in relation to Parkinson’s disease,” says Riise.
Riise underlines the fact that “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.”
Copy number mutations implicate excess production of α-synuclein as a possibly causative factor in Parkinson’s disease (PD). Using an unbiased screen targeting endogenous gene expression, we discovered that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene (SNCA). β2AR ligands modulate SNCA transcription through histone 3 lysine 27 acetylation of its promoter and enhancers. Over 11 years of follow-up in 4 million Norwegians, the β2AR agonist salbutamol, a brain-penetrant asthma medication, was associated with reduced risk of developing PD (rate ratio, 0.66; 95% confidence interval, 0.58 to 0.76). Conversely, a β2AR antagonist correlated with increased risk. β2AR activation protected model mice and patient-derived cells. Thus, β2AR is linked to transcription of α-synuclein and risk of PD in a ligand-specific fashion and constitutes a potential target for therapies.
Shuchi Mittal, Kjetil Bjørnevik, Doo Soon Im, Adrian Flierl, Xianjun Dong, Joseph J Locascio, Kristine M Abo, Elizabeth Long, Ming Jin, Bing Xu, Yang K Xiang, Jean-Christophe Rochet, Anders Engeland, Patrizia Rizzu, Peter Heutink, Tim Bartels, Dennis J Selkoe, Barbara J Caldarone, Marcie A Glicksman, Vikram Khurana, Birgitt Schüle, David S Park, Trond Riise, Clemens R Scherzer