RARE DISEASE RESEARCH & TRAINING

IPRD funded research by Michelle Parvatiyar, Ph.D.

Duchenne muscular dystrophy is a lethal X-linked genetic disorder that affects 1:3500 live male births. The disease is caused by mutations in the dystrophin gene encoding the dystrophin protein, which is required for maintaining muscle cell structure and muscle fiber integrity. Inflammation plays a significant role in the pathogenesis, contributing to ongoing muscle damage. Loss of muscle cell integrity triggers inflammation and chronic inflammation further exacerbates muscle deterioration. Nuclear factor kappa-B (NF-kB) is an essential transcription factor controlling the inflammatory response. Therefore, NF-kB inhibitors have attracted considerable attention as potential therapies. However, clinical trials of various NF-kB inhibitors have produced mixed results as these drugs also influence other cellular signaling pathways. Unfortunately, other anti-inflammatory drugs have been ineffective in significantly halting DMD progression. These observations suggest that further refinement of the approaches to target the NF-kB pathway is required. This research project will focus on a less well characterized “non-canonical” NF-kB signaling pathway that drives tissue-damage-induced inflammation, as a first step toward identifying novel targets for small molecule drugs that can reduce muscle damage produced by inflammation.