Development of a Nurr1 Activator as a Novel Therapeutic for Parkinson’s Disease

Study Rationale: Nurr1 is a protein that works in the nucleus of dopamine-producing nerve cells in the brain to keep these cells functioning normally. Emerging evidence suggests that impaired function of Nurr1 may contribute to the pathology of Parkinson’s disease (PD). ATH-399A is an activator of Nurr1 that may improve PD symptoms. Before we test ATH-399A on people with PD, we will first give the drug to healthy volunteers to study its safety and assess how the body handles ATH-399A, how long it remains in circulation and how it is metabolized and eliminated.

Hypothesis: We hypothesize that the drug ATH-399A will be safe and well tolerated in healthy volunteers and that increasing its dosage will increase its blood levels proportionately.

Study Design: We will begin by testing small groups of healthy volunteers with a single, oral dose of ATH-399A. We will observe the volunteers and draw blood to check the drug levels before administering a higher dose. Next, we will assess whether healthy older adults respond the same way to a single dose, and whether eating food beforehand changes their response. Lastly, we will test small groups of healthy adults to see how they respond to repeated daily doses by mouth for several days to make sure the drug is safe and well tolerated and results in stable blood levels.

Impact on Diagnosis/Treatment of Parkinson’s Disease: This drug might be used early after the diagnosis of PD to boost the activity of dopamine cells and slow the progression of the disease.

Next Steps for Development: If ATH-399A is found to be safe and well tolerated and can achieve stable blood levels after multiple doses in healthy volunteers, we would be able to go to a phase 2 study to test the response in people with PD.

Trial Phase: Phase 1 trial