Protein alpha-synuclein clumps in the brains of people with Parkinson's disease (PD), forming Lewy bodies. Recent studies have suggested that beta-2 adrenoreceptor agonists -- drugs used to treat asthma and other breathing disorders -- can decrease alpha-synuclein production and the risk of developing PD. In this study, we will examine the ability of clenbuterol, a beta-2 adrenoreceptor agonist, to reduce alpha-synuclein clumping in a pre-clinical model with Parkinson's features.
We hypothesize that clenbuterol can decrease alpha-synuclein production and prevent formation of clumps resembling Lewy bodies in the brains of pre-clinical models with Parkinson's features.
Firstly, we will identify the dose of clenbuterol that moderately (from 30 percent to 50 percent) decreases alpha-synuclein production in pre-clinical models. We will then treat pre-clinical models of Parkinson's with alpha-synuclein clumps with clenbuterol. Clenbuterol will be given either before or after the clumps appear to examine its potential preventative and disease-modifying effects, respectively. We will focus on evaluating the ability of clenbuterol to reduce the formation of alpha-synuclein clumps resembling Lewy bodies in the substantia nigra, a brain region damaged in PD. If the treatment indeed prevents the formation of clumps, the mechanism of action of clenbuterol will be examined.
Impact on Diagnosis/Treatment of Parkinson's disease:
Moderately decreasing alpha-synuclein production may delay the onset and/or slow the progression of Parkinson's. If our hypothesis is correct, the results of this study will provide additional evidence in support of clinical trials of beta-2 adrenoreceptor agonists as a disease-modifying therapy for Parkinson's disease.
Next Steps for Development:
The next step would be to evaluate the effects of beta-2 adrenoreceptor agonists on neurodegeneration. In those studies, we would use drugs in doses sufficient to limit the formation of clumps in the cells of the substantia nigra. The proposed studies would assess the effects of treatment over the course of six months.