Could salbutamol be repurposed for treatment of Parkinson’s disease?
The β2‑adrenoreceptor (β2AR) agonist salbutamol, a brain-penetrant asthma medication, appears to reduce the risk of developing Parkinson’s disease (PD), possibly through the epigenetic suppression of SNCA—the gene that encodes α-synuclein, according to a study.
Given that high expression of the SNCA is a risk factor for PD, researchers hypothesized that chemical compounds designed to reduce the transcription of the SNCA gene could prevent or slow down the disease process in selected patients.
To test the hypothesis, researchers went on to assay the relative endogenous SNCA mRNA expression using an unbiased screen targeting endogenous gene expression and found that the β2AR was a regulator of the SNCA.
Next, they examined the pharmaceutical history of more than 4 million Norwegians over an 11-year period. The β2AR agonist salbutamol showed a protective effect against the risk of developing PD (rate ratio, 0.66; 95 percent CI, 0.58 to 0.76). In contrast, a β2AR antagonist was associated with increased PD risk.
Furthermore, β2AR agonist treatment led to SNCA expression reductions in a mouse model of PD and in PD patient-derived cells.
“Our study presents a path to drug development that is distinct from traditional approaches,” researchers said, adding that targeting the endogenous expression of a human disease gene represents a useful strategy for other diseases attributed to copy number variation or regulatory variants.
“Evaluation in additional populations and in clinical trials will be required to determine whether the insights gained in this work can be translated to patients with PD,” they pointed out.