Genetic repair of muscular degeneration associated with duchenne muscular dystrophy

The National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded the Board of Trustees of Illinois State University $544,734 on August 1, 2026, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846) to investigate smooth muscle pathology mechanisms in Duchenne muscular dystrophy.

The project, running through July 31, 2029, uses C. elegans as a model system to characterize smooth muscle dysfunction associated with DMD, addressing a clinical gap where existing gene therapy and corticosteroid treatments improve skeletal and cardiac muscle function but leave 74 percent of patients with life-limiting bladder dysfunction and 68 percent with severe bowel complications. In Aim 1, the research team will characterize smooth muscle dysfunction using behavioral analysis, multi-compartment calcium imaging, and transcriptomic profiling. In Aim 2, the team will evaluate therapeutic efficacy across muscle types, testing microdystrophin constructs and corticosteroids for differential rescue patterns. The work includes validation in human smooth muscle cell systems and will provide hands-on research training for over 70 undergraduate students.

Performance occurs in Normal, Illinois.

Abstract

Duchenne muscular dystrophy (DMD) is a severe genetic disorder that causes progressive muscle degeneration, affecting approximately 1 in 5,000 males. IT is caused by mutations in the gene encoding dystrophin, a structural protein critical for maintaining muscle fiber integrity. While significant progress has been made with gene therapy and corticosteroids, these treatments focus on skeletal and cardiac muscle while 74% of patients develop life-limiting bladder dysfunction and 68% suffer severe bowel complications. There remains a critical need to understand smooth muscle pathology mechanisms affecting three-quarters of DMD patients. This project investigates smooth muscle dysfunction using C. Elegans, the first platform enabling systematic cross-tissue comparison within individual animals. Building on discoveries from our prior NIH-funded work, we focus on smooth muscle systems controlling gastrointestinal function. Our preliminary data show that corticosteroids rescue striated but not smooth muscle dysfunction, directly mirroring clinical observations where patients show improved locomotion but persistent gastrointestinal problems. We use C. Elegans alongside human smooth muscle cell validation systems. In aim 1, we will characterize smooth muscle dysfunction using behavioral analysis, multi-compartment calcium imaging, and transcriptomic profiling. In aim 2, we will evaluate therapeutic efficacy across muscle types, testing microdystrophin constructs and corticosteroids for differential rescue patterns. This work seeks to define smooth muscle pathology mechanisms that remain therapeutically unaddressed. By establishing the first cross-tissue platform for smooth muscle DMD research, IT will identify tissue-specific therapeutic requirements for comprehensive treatments. Additionally, IT will provide research training for 70+ undergraduate students through direct hands-on involvement in all research phases, preparing the next generation of scientists with cutting-edge microscopy, behavioral, and translational research techniques while fulfilling R15 area objectives of strengthening the research environment at undergraduate-focused institutions.