D-512: a Novel, Multifunctional D2/D3 Receptor Agonist for the Treatment of Parkinsonís Disease
Rapid Response Innovation Awards, 2014
Study Rationale: † † † † † † † † ††
New drugs for the treatment of Parkinsonís disease (PD) that reduce symptoms and protect remaining neurons are desperately needed. This work examines a novel, multifunctional dopamine agonist, D-512, that has been shown to provide potential anti-parkinsonian benefit and protect neurons in pre-clinical models of PD.
We will test the hypothesis that the multifunctional dopamine agonist D-512 will provide superior, long-lasting symptom relief in a parkinsonian model of PD.
Pre-clinical models will be administered either the novel D2/D3 receptor agonist D-512 or the commercially available D2/D3 receptor agonist ropinirole over 22 days. Throughout this time, the models will be examined for motor performance, drug-induced rotations and dyskinesia. At the end of the study, we will verify dopamine lesion status. In another set of models, drug pharmacokinetics will be determined in brain and plasma. ††
Impact on Diagnosis/Treatment of Parkinsonís Disease: † † † † † ††
These pre-clinical studies will support D-512 as a new therapeutic option for PD treatment by demonstrating its superior properties in a validated PD model over an often-used dopamine agonist.
Next Steps for Development:
This initial work will spur several future lines of inquiry and development, including key pre-clinical studies of neuroprotection, drug properties and the utility of D-512 for people with PD.
New treatments for Parkinsonís disease (PD) that provide both symptom relief and slow or halt disease progression are desperately needed, but as of yet are unrealized. Recently, the co-PI, Dr. Aloke Dutta developed a candidate molecule D-512 that displayed impressive, though preliminary symptomatic and neuroprotective characteristics. In order to extend these initial promising results, we employed a pre-clinical model of PD that allowed us to test the potential anti-parkinsonian effects of D-512 against the clinically used drug ropinirole. Our studies demonstrated that D-512 conveyed significant, lasting and superior anti-parkinsonian benefit on several validated motor assays, compared to ropinirole. Moreover, D-512 appeared to have a low liability for drug-induced side effects like dyskinesia. Such findings implicate its potential as a novel pharmacological treatment of PD. Translationally, these results strongly implicate the utility of further investigation and development of D-512.
Professor of Psychology at Binghamton University
Location: Binghamton, New York, United States
Professor of Medicinal Chemistry and Neuropharmacology at Wayne State University
Location: Detroit, Michigan, United States