Promising Outcomes of Original Grant:
The drug clenbuterol, a beta-2 adrenoreceptor agonist, has been shown to decrease alpha-synuclein expression and to be neuroprotective in some models. Our results have shown clenbuterol administration leads to a moderate decrease in alpha-synuclein mRNA and soluble protein in the substantia nigra of models. Though decreases are observed, they are lower than what has been shown in other models and may not be sufficient be biologically relevant.
Objectives for Supplemental Investigation:
Moderate decreases in alpha-synuclein mRNA and soluble protein suggest that administration of a sufficient dose of clenbuterol or other beta-2 adrenoreceptor agonist could be used to further decrease alpha-synuclein. Through increasing the dose of clenbuterol, the addition of a new dosing paradigm, and taking a multi-species approach, we intend to determine if alpha-synuclein can be decreased to a biologically meaningful level.
Importance of This Research for the Development of a New PD Therapy:
A potential therapeutic to decrease alpha-synuclein could be beneficial in delaying the onset or slowing the progression of PD. Results from these studies could provide evidence for or against future studies focusing on neurodegeneration and/or clinical trials for beta-2 adrenoreceptor agonists in PD.