Study Rationale: Mitochondria are subcellular structures that produce energy and help regulate the movement of calcium ions that continually flow into brain cells when they are active, ions that can become toxic if not removed. In Parkinson’s disease (PD), mitochondria can become overloaded with calcium ions, triggering the opening of a large pore or hole in the mitochondrial membrane, leading to cell death and the loss of dopamine-producing neurons. NRG Therapeutics is developing a novel drug that can enter the brain and inhibit the opening of this pore and thus prevent the death of brain cells.
Hypothesis: We hypothesize that NRG Therapeutics’ novel drug candidate will prove safe for dosing in humans, and we anticipate being able to identify methods that can be used in human clinical trials to demonstrate that the drug has entered the brain and is biologically active.
Study Design: The project will be split into four key objectives: 1) Developing a safe, low-dose radiotracer that can be used to demonstrate that our drug enters the brain. 2) Manufacturing large multi-kilogram batches of the drug that can be used for testing in preclinical animal toxicology studies and for dosing in human. 3) Completing regulated animal toxicology studies to determine if the drug is safe to be dosed in human. 4) Identifying and validating new methods to determine if the drug produces a biological effect in the brain consistent with its proposed mechanism of action.
Impact on Diagnosis/Treatment of Parkinson’s disease: NRG Therapeutics is developing a new drug that will protect mitochondria and prevent death of dopamine-producing cells in the brain. If this can be achieved, the drug will have the potential to slow or halt the progression of disease in the majority of people with PD.
Next Steps for Development: The next step would be initiation of clinical trials in human — first, to confirm the drug is safe and well tolerated and importantly enters the brain in healthy volunteers. If successful, the drug will then be tested in a small number of people with PD.