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

Surgical approaches to treatment of Parkinson’s disease using deep brain stimulation and corrective lesions provide valuable insights into novel approaches for treatment of this disorder by altering activity in brain circuits that control motor function. This program seeks to develop a novel drug therapy for PD that provides sustained Symptoms & Side Effects relief by inducing changes in brain function currently achieved with surgical approaches.

Project Description: 
We have identified a neurotransmitter receptor that reduces activity of a brain pathway that is overactive in PD patients. We used a library of 1.2 million drug-like molecules we to identify molecules that increase activity of this neurotransmitter receptor. We will now use a combination of medicinal chemistry, molecular biology, and animal studies to engineer these molecules so that they have all of the properties needed for use as a drug. This requires an intense team effort by chemists, molecular pharmacologists, behavioral scientists, drug disposition scientists and engineers. This team will use an iterative compound synthesis and testing approach to engineer a molecule that has all the properties required to be tested in humans as a new drug for treatment of Parkinson’s disease.

Relevance to Diagnosis/Treatment of Parkinson’s Disease: 
PD is treated with medicines that replace the neurotransmitter dopamine that is lost in Parkinson’s patients. These medicines have severe adverse effects and lose reliable efficacy as the disease progresses. This program endeavors to develop a new medicine that could provide sustained reliable Symptoms & Side Effects relief at all stages of PD. If successful, this could provide a transformative advance in treatment of PD.

Anticipated Outcome: 
If successful, this program will deliver a drug candidate and backup compounds that can be tested for efficacy in treatment of PD. In addition, the studies will provide valuable new information on the impact of regulation of transmission in an identified brain circuit impacted by PD on symptoms of the disease. This could provide a major advance in stimulating other treatment strategies that are focused on altering activity in this brain circuit.


  • P. Jeffrey Conn, PhD

    Nashville, TN United States

  • C. David Weaver, PhD

    Nashville, TN United States

  • Colleen Niswender, PhD

  • Carrie K. Jones, PhD

    Nashville, TN United States

  • Yoland Smith, PhD

    Atlanta, GA United States

  • Craig W. Lindsley, PhD

    Nashville, TN United States

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