AMP – Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease

Date:  April 2013

Award:  Doctoral award of $17,500 per year for three years; Canadian Institutes of Health Research matches these funds.  Total award is $105,000.

AMP-Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease

Alexander Green, M.Sc. (candidate); Mark Tarnopolsky, M.D., Ph.D., FRCP(C) (supervisor)
Neuromuscular and Neurometabolic Clinic,
McMaster University Medical Center 

The study investigates the activation of AMP-Activated Protein Kinase (AMPK) as a therapy to correct functional deficits in cells isolated from patients with mitochondrial disease. When active, AMPK can induce the generation of new mitochondria and the degradation of dysfunctional mitochondria. AMPK is naturally activated under energy-depleted conditions. The most well studied energy-depleted conditions are starvation and exercise. The pharmaceutical drug, AICAR, can also activate AMPK and is therefore also considered an exercise mimetic. Thus, AICAR is a potential pharmaceutical treatment for the functional deficits associated with mitochondrial disease. Furthermore, this study will use direct measurements of cellular health/function. We will observe whole cell respiration and mitochondrial membrane potential using fluorometric assays on a fluorescence plate reader and flow cytometer. The direct investigation of therapeutic strategies on cells, from patients with mitochondrial disease, and their functional capacity make this study directly relevant to the Mitochondrial Disease Research Priority Area.