Common asthma medication may lower Parkinson’s disease risk
Original article: b2-andrenoreceptor is a regulator of the a-synuclein gene driving risk of disease, Science: September 1, 2017
Salbutamol, one of the most common treatments for asthma, may reduce the risk of developing Parkinson’s disease.
Why is it important?
Drugs developed to treat one disease often hold promise for treating other diseases. These results lay the foundation for further investigation of salbutamol while also revealing an important molecular mechanism in Parkinson’s.
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“The trial provided additional support for further study of Exenatide and other GLP-1 agonists (a common category of diabetes drugs) for the treatment of Parkinson’s disease. Results from this study as well as previous work is promising; however, more research is needed to fully understand if Exenatide is slowing the disease’s progress.” Dr. Patrik Brundin
Exenatide is already approved to treat diabetes. However, until additional studies are completed, the authors urge caution in adding Exenatide to Parkinson’s disease treatment regimens.
Clumps of abnormal alpha-synuclein proteins in brain cells are a hallmark of Parkinson’s disease. It is thought that problems with cells’ ability to produce energy interferes with normal cellular housekeeping, allowing alpha-synuclein to stick together and build up. Over time, these clumps, called Lewy bodies, create inflammation and damage or kill the cells, leading to the onset of Parkinson’s symptoms.
Scientists have long searched for ways to clear abnormal alpha-synuclein out of brain cells in an effort to prevent inflammation and cell death. To this end, the study authors grew brain cells in the laboratory and treated them with more than 1,100 difference substances, including medications and vitamins, to see which ones impacted the levels of alpha-synuclein.
Salbutamol, a common asthma treatment, appeared to affect the activity of the alpha-synuclein gene, which controls production of the protein.
To see how salbutamol use might affect risk, the authors analysed the Norwegian Prescription Database, which contrains information on all drugs prescribed in Norway since 2004. They determined that people who had taken salbutamol at least once were about a third less likely to develop Parkinson’s than those who had never used salbutamol.
Preclinical research into the potential of Salbutamol as a possible treatment for Parkinson’s before symptoms appear using models of Parkinson’s is required before this can be tested in clinical trials. Safety also needs to be tested in Parkinson’s models due to the cardiovascular risks associated with this drug.
High expression of the a-synuclein gene is a risk factor for Parkinson’s. Research has shown that the β2-adrenoreceptor (β2AR) is involved in modulating the ‘epigenetics’ of the alpha-synuclein gene. Epigenetics refers to the set of controls that regulate how genes are expressed without actually changing the genetic instruction manual itself. Activation of this receptor can suppress the production of the alpha-synuclein protein. The study discussed here supports the role of β2AR as Salbutamol is a β2AR agonist (or activator) and the study found that people who had taken Salbutamol for other medical problems have a reduced risk of Parkinson’s.
Original article: Mittal S, Bjørnevik K, Im DS, Flierl A, Dong X, Locascio JJ, Abo KM, Long E, Jin M, Xu B, Xiang YK, Rochet JC, Engeland A, Rizzu P, Heutink P, Bartels T, Selkoe DJ, Caldarone BJ, Glicksman MA, Khurana B, Schüle B, Park DS, Riise T, Scherzer CR. September 1, 2017. b2-andrenoreceptor is a regulator of the a-synuclein gene driving risk of disease