Targeting M4 Muscarinic Receptors for the Treatment of Levodopa-induced Dyskinesia
Dyskinesia Challenge, 2015
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.
We hypothesize that M4R modulators blunt atypical, levodopa-evoked changes and reduce abnormal involuntary movements.
In dyskinetic pre-clinical models, we will test if boosting M4R signaling will ease abnormal involuntary movements.
Impact on Diagnosis/Treatment of Parkinsonís 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.
Research Associate Professor at Northwestern University Feinberg School of Medicine
Location: Chicago, Illinois, United States
Professor and Chair of the Department of Physiology at the Feinberg School of Medicine and Director of the Morris K. Udall Research Center of Research Excellence for Parkinson's Disease at Northwestern University
Location: Chicago, Illinois