Study Rationale: Overwhelming evidence indicates that mitochondrial dysfunction contributes to the development of Parkinson’s disease (PD). We discovered that drugs that activate the enzyme AMPK prevent tissue damage caused by mitochondrial dysfunction. Our goal is to develop brain-permeable activators of AMPK and test whether they can prevent neurodegeneration in a preclinical mouse model of PD.
Hypothesis: We hypothesize that activating the enzyme AMPK can reduce neurodegeneration in a mouse model of PD.
Study Design: In the first part of the study, we will test the drug-like and safety properties of our brain-permeable AMPK activating compounds and identify the best one. In the second part of the study, we will test how well our best brain-permeable drug improves the neurological defect in a mouse model of PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: Because all people with PD have underlying mitochondrial dysfunction, all of these individuals, regardless of primary etiology, are expected to benefit from treatment with an AMPK activator.
Next Steps for Development: Future studies will involve testing our drug in additional preclinical models of PD, including mice with defects in LRRK2 and PINK, and those that overproduce alpha-synuclein. We will also perform comprehensive pre-clinical pharmacology and toxicology studies across different animal species, including non-human primates, in preparation for IND filing.