Grant: CIHR Fellowship

The Nuclear Factor-kB (NF-kB) pathways form a signaling complex that is critical for normal skeletal muscle function and is important in promoting recovery in response to muscle injury. Furthermore, there is strong evidence that too much NF-kB activity is detrimental to normal skeletal muscle function and can contribute to diseases such as the common genetic disorder, Duchenne muscular dystrophy (DMD). As such, NF-kB has become an attractive drug target for the treatment of muscle diseases. Our lab has found that the cellular inhibitor of apoptosis 1 (cIAP1) can control NF-kB signaling to benefit skeletal muscle function. This discovery has raised the exciting possibility that cIAP1 may be a potential therapeutic target for a number of muscle diseases that are caused or worsened by over-activation of NF-kB. Since we have several drugs that effectively and specifically remove cIAP1, we will evaluate their therapeutic potential in mdx mice, the mouse model for DMD. We will also clarify the mechanism of action of these drugs by examining how they change NF-kB activity in dystrophic muscle. Our findings have the potential to improve muscle structure and function and thus the quality of life of patients living with DMD.