Parkinson´s disease is a chronic disease with unknown causes. The disease destroys the brain cells that control body movements. Shivering, stiff arms and legs and poor coordination are typical symptoms of Parkinson´s. The symptoms may develop slowly, and it sometimes takes time to make a correct diagnosis.

Lewy bodies - abnormal clumps of alpha-synuclein protein that accumulate in the brain - are a hallmark of Parkinson's disease (PD). Traditional drug development approaches for PD have focused on clearing alpha-synuclein from the brain or on preventing its downstream effects.

But researchers want to prevent alpha-synuclein from accumulating in the first place. To do so, the team searched for drugs that turn down alpha-synuclein production. They then tested the drugs in mice and stem cells and studied the health records of millions of people living in Norway. The results of their efforts, which point to a new drug development path for PD, are published in Science.

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. Authors show that the β2AR agonist salbutamol, a brain-penetrant asthma medication, was associated with reduced risk of developing PD. Conversely, a β2AR antagonist correlated with increased risk. β2AR activation protected model mice and patient-derived cells.

Researchers have completed a large study that included data from the Norwegian Prescription Database, in cooperation with researchers at Harvard University. They analyzed more than 100 million Norwegian prescriptions registered since 2004.

They found that these patients were significantly less likely to develop PD - PD risk was reduced by 34 percent for those taking the asthma drug compared to those who were not.

Conversely, people taking propranolol - a hypertension drug that increased alpha-synuclein production in cultured cells - were at greater risk for developing PD.

The 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 the researcher. The study was published in the journal Science.

 

http://www.uib.no/med/110179/astmamedisin-halverer-parkinsons-risiko

http://science.sciencemag.org/content/357/6354/891