Researchers have found that compounds in certain drugs used in the treatment of asthma, may also have beneficial effects in Parkinson’s disease.

In this study, a large group of researchers from the USA and Norway published the results of a very interesting project. Initially, they wanted to determine compounds which would reduce the production of the toxic protein alpha-synuclein in neurons - believed to be a major contributory factor in the development of Parkinson's. The investigators grew neurons that produced the human version of alpha synuclein and went on to screen over a 1,000 compounds to investigate their impact on these cultured neurons. From these, they discovered 35 compounds which reduced the levels of alpha-synuclein by more than 35%. One of these compounds was the beta2-adrenoreceptor agonist metaproterenol. This drug is primarily used to treat conditions of the lungs such as asthma causing smooth muscle fibres to relax.

Beta2-adrenoreceptor agonists bind to and activate the beta2-adrenergic receptor inside the neurons. The Beta2-adrenergic receptor interacts with a chemical called epinephrine, which is a neurotransmitter like dopamine. Epinephrine binds to the Beta2-Adrenergic receptor, and activates it. Thus, beta2-adrenoreceptor agonists effectively behave in the same way as epinephrine.

In the study, the neurons treated with the beta2-adrenoreceptor agonists generated less alpha-synuclein. Further investigations of neurons in mouse models injected with beta2-adrenoreceptor agonists found that those cells also produced less alpha-synuclein. Interestingly, they also noted that in mice that did not have any beta2-adrenergic receptor, the levels of alpha-synuclein in the brain were twice as high as normal.

The researchers then studied people treated with beta2-adrenoreceptor agonists by looking at the Norwegian Prescription Database which contains the complete records of all prescribed drugs dispensed at pharmacies to every individual in Norway since 2004.

They looked at prescriptions of the beta2-adrenoreceptor agonist, Salbutamol to see whether use of this drug could reduce the risk of developing Parkinson’s and found that Salbutamol was associated with decreased risk of developing Parkinson’s disease by over 30%. The researchers also asked the reverse question: does blocking beta2-adrenergic receptor (with an antagonist drug) increase one’s risk of developing Parkinson’s disease?

Propranolol is often called a ‘beta-blocker’ because it blocks the beta2-adrenergic receptor. This beta2-adrenoreceptor 'antagonist' is commonly used to treat high blood pressure and essential tremor. In their analysis, the researchers found that Propranolol was associated with a two-fold increase in the risk of developing Parkinson’s disease. See graphic:

Graphic: Science article

As the graph above shows, those individuals on a high defined daily doses (DDD) of Salbutamol (the red line on the left graph) had a lower risk of developing Parkinson’s than those who were administered low levels of Salbutamol (the green line – which does not differ from the general population level of risk (blue line)). In the graph on the right the 9,339 individuals treated with Propranolol (green line) had a higher risk of developing Parkinson’s disease than the general population.

There is clearly an interesting biological effect suggesting that this class of drugs is worthy of further investigations. However, as is the case with many trial results of small studies and where it is not clear if the molecule/drug is having a specific effect on the overall condition, there needs to be independently replicated trials before proper conclusions can be made.

Note: Salbutamol has been discussed at our recent Linked Clinical Trials meeting 2017

Thanks to The Science of Parkinson's Disease - Dr Simon Stott