Grant: Project Grant

PARPs are proteins that change other proteins, in a process called PARylation, using Vitamin B3. To kill cancer, drugs that stop PARylation (PARP inhibitors) have recently been developed. Since 2019, the use of these drugs have doubled annually. In 2019, Canada spent $16.8 million CAD on PARP inhibitors and this increased to $32 million CAD in 2020. PARP inhibitor use is within the top 100 most expensive drug categories in Canada and in 2022 represented a $6 billion USD market. It's predicted it will increase to $19.4 billion USD in 2031. In unpublished work, we found that PARylation inhibitors had a greater proportion of muscle side effects versus a common cancer therapy (cisplatin). Despite these side effects, very little is known about PARylation in muscle health. Muscle affects many aspects of human health including locomotion, breathing and metabolism. Further, maintaining muscle during cancer is associated with better health post-cancer. Therefore, maintenance of muscle function is essential to a healthy lifestyle and aging. Previously, our lab found that PARylation is more active in muscular diseases, like muscular dystrophy, and that supplementation with Vitamin B3 improved muscle function in this disease and in aging. In this proposal, we will use pharmaceuticals and genetic interventions to alter PARylation in muscle and examine the effects on muscle health during cancer.