Targeting M4 Muscarinic Receptors for the Treatment of Levodopa-induced Dyskinesia

Study Rationale:                   
Levodopa-induced dyskinesia is thought to stem from sustained stimulation of D1 dopamine receptors (D1Rs). One potential strategy for diminishing excessive D1R signaling is to increase the activity of opposing M4 muscarinic receptors (M4Rs), which inhibits the primary signaling target of D1Rs.

Hypothesis:
We hypothesize that M4R modulators blunt atypical, levodopa-evoked changes and reduce abnormal involuntary movements.

Study Design:
In dyskinetic pre-clinical models, we will test if boosting M4R signaling will ease abnormal involuntary movements.

Impact on Diagnosis/Treatment of Parkinson’s disease:              
These studies should provide a solid foundation for further translational studies aimed at developing adjunct therapies that alleviate levodopa-induced dyskinesia.

Next Steps for Development:
Any insights gained from these studies should be followed up in a larger pre-clinical model.