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Funded Studies

Evaluating the Efficacy of a mGluR5 Modulator in Preclinical Models of Parkinson’s Disease

Study Rationale: Parkinson’s disease (PD) is one of many neurodegenerative diseases that are characterized by the buildup of misfolded protein aggregates in the brain. Preclinical data suggest that cellular prion protein (PrPC) and metabotropic glutamate receptor 5 (mGluR5) receptors are responsible for inducing the damaging effect of such toxic aggregates. A unique mGluR5 modulator has been shown to reverse behavioral and pathological defects in numerous models of Alzheimer’s disease (AD) by blocking the toxic effects of amyloid-beta accumulation. Preliminary evidence suggests it might have similar effects in preclinical models of PD.

Hypothesis: We hypothesize that this mGluR5 modulator can also block the toxic effects of alpha-synuclein accumulation in PD and lead to a promising treatment.

Study Design: We will evaluate the efficacy of our mGluR5 silent allosteric modulator in the prevention and reversal of disease phenotypes in multiple preclinical mouse models of PD, testing both behavioral and pathological preservation and recovery of neuronal connections.

Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, this compound offers promise as a disease modifying therapy and may be capable not only of preventing disease progression, but also restoring motor function and cognition.

Next Steps for Development: Phase 1 safety and pharmacokinetic studies for this compound are currently underway in healthy volunteers; if our study is successful, the next step would therefore be a Phase 2a clinical trial in people with PD.


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