Professor Patrik Brundin, Van Andel Institute

Project in context: The mitochondria is like the "power house" of the cell , producing energy. If the Mitochondria are affected by disease they cannot produce energy for the cells, and in turn energy for the body's organs. Mitochondria are found in every cell of the human body except red blood cells. Mitochondria converts the energy of food molecules into the ATP that powers most cell functions.

Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function.
Symptoms of Mitochondrial dysfunction include loss of muscle coordination, muscle weakness, visual problems, hearing problems, gastrointestinal disorders, neurological problems, autonomic dysfunction and dementia. Many diseases of aging are caused by defects in mitochondrial function, including Type 2 diabetes, Parkinson's, atherosclerotic heart disease, stroke, Alzheimer's disease, and cancer.

What is this project? Professor Brundin is proposing using a novel type-2 diabetes drug (MSDC-0160) to adapt mitochondrial function to see if this will be neuroprotective in two different models of Parkinson’s. He is using two different models to show clearly how this drug works, and regulators require two models to be used, so laying the groundwork for moving this into trials.
In this project he will use two models which share features regarding pathology and degeneration patterns (similar to the ones observed in PD patients) but have been generated in two different ways. One displays mitochondrial deficits caused by a genetic deletion, the other is the result of excessive production of alpha synucleinn in the substantia nigra that eventually clumps together becoming toxic, causing dopaminergic cell death.

Prof Brundin wants to prove that MSDC-0160 improves mitochondrial activity and stops the pathways associated with Parkinson’s (preventing alpha synuclein aggregation). If successful, this project will prove that in models of Parkinson’s by using MSDC-0160 will modify the mitochondrial target which has disease-modifying effects in Parkinson's.