When people with asthma have trouble breathing, they may reach for an inhaler containing salbutamol, a drug that expands the airways. Salbutamol may have another beneficial effect—protecting against Parkinson’s disease. Individuals who inhaled the highest doses of salbutamol were about half as likely to develop the devastating neurological condition as those who didn’t take the drug, a study reveals.
“I’m sure it’s going to be a landmark paper,” says neurologist Joseph Jankovic of Baylor College of Medicine in Houston, Texas, who wasn’t involved in the research.
In Parkinson’s disease, gobs of the protein α-synuclein accumulate in certain brain cells and may kill them. Scientists have tried to craft drugs that speed the elimination of the protein or prevent it from clumping. Neurologist and genomicist Clemens Scherzer of Harvard Medical School in Boston and colleagues decided to try a different strategy. “We wanted to find a drug that could turn down the production of α-synuclein,” he says.
To identify promising compounds, the team grew human nerve cells in the lab and tested whether more than 1100 medications, vitamins, dietary supplements, and other molecules altered their output of α-synuclein. Three of the drugs that cut the protein’s production, including salbutamol, work by stimulating the b2-adrenoreceptor—a molecule on some body cells that triggers a variety of effects, including relaxing the airways. The researchers found that these drugs appear to alter how tightly the DNA containing the α-synuclein gene coils, and thus whether the gene is active.
Salbutamol is one of the world’s most frequently used drugs, and the researchers wondered whether people who took it were less likely to have Parkinson’s disease. “You need to have very large prescription databases with many years of follow-up to do this analysis,” Scherzer says. The researchers found such a database in Norway, which keeps records of all drugs prescribed for each of its 4.6 million residents. The disease was rare. Roughly 0.1% of people who didn’t use the drug developed Parkinson’s disease. The rate among people who used salbutamol was less than 0.04%. After the researchers corrected for factors such as age and education, they determined that Norwegians who had taken salbutamol at least once in their lives were about one-third less likely to develop Parkinson’s disease.
How much protection salbutamol provided depended on the dosage. Compared with Norwegians who didn’t use the drug, people who took the highest doses between 2004 and 2007 were about half as likely to get the disease in the subsequent 7 years. In contrast, patients who took the lowest doses had only slightly lower odds of developing Parkinson’s disease in that period, the researchers report online today in Science.
The results are “fascinating” and “come out of the blue,” says neurologist Anthony Lang of the University of Toronto in Canada. However, he has misgivings about the analysis of the Norwegian data because salbutamol’s influence on α-synuclein appears to be so powerful that it’s surprising we ever see a Parkinson’s patient with asthma, he says. Given that some people do have both diseases, other factors that correlate with salbutamol use might be affecting Parkinson’s disease susceptibility. “We have to take other possible explanations into account,” he says.
Researchers aren’t sure about the best way to harness the results to benefit patients. Clinical trials of salbutamol or related drugs are one possibility. However, none of these drugs is optimized to enter the brain, says neuroscientist Andrew West of the University of Alabama in Birmingham. “The drugs that are going to be ideal for targeting [α-synuclein] have yet to be developed.”
Scherzer says that any clinical trials are “a few years off.” He notes that 16 recent trials of potential Parkinson’s disease treatments have failed. He and his colleagues don’t want to have No. 17.