Supplement to 'Discovery of mGluR4 Potentiators for Symptoms & Side Effects and Disease-Modifying Treatment of PD'

Promising Outcomes of Original Grant:
Activation or potentiation of metabotropic glutamate receptor 4 (mGluR4) is a promising new strategy for both Symptoms & Side Effects and disease-modifying treatment in Parkinson’s disease (PD). Our team has now developed new small molecule drug candidates for mGluR4 which are orally active in pre-clinical models of Parkinson’s disease and possess the balanced properties necessary to administer to patients.

Objectives for Supplemental Investigation:
The studies we will now perform are critical for selecting the best compound to progress to a clinical trial. We will profile our best compounds to determine which drug candidates have the best efficacy in a variety of pre-clinical PD models as well as assess their safety and pharmacokinetic properties. These studies will inform both clinical trial design in terms of the dosing regimen as well as the potential for additive effects of mGluR4 PAMs with currently used antiparkinsonian drugs.

Importance of This Research for the Development of a New PD Therapy:
Unlike most currently available PD drugs, drugs targeting mGluR4 represent a completely novel mechanism for PD treatment. We anticipate that compounds developed within our program will be “first in class” and will provide important insight into a presently unexplored area for PD therapy. We are also hopeful that drugs targeting mGluR4 will slow disease progression or possibly treat other symptoms of PD such as anxiety or depression, which could greatly improve the quality of life for patients living with PD.