Federal Project Grant Award Summary

The University of Arizona received a $578,565 Project Grant awarded July 10, 2026, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846) administered by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The grant supports a five-year research initiative (completion date June 30, 2031) investigating the role of slow myosin binding protein-C (SMYBP-C) in the pathogenesis of distal arthrogryposis (DA), a genetic skeletal muscle disorder characterized by congenital joint contractures, muscle weakness, and reduced mobility. The research employs knock-in mouse models carrying mutations in the MYBPC1 gene to elucidate the molecular mechanisms by which SMYBP-C mutations disrupt actin-myosin interactions and calcium regulation in striated muscle, with the objective of identifying novel therapeutic targets for a condition currently lacking FDA-approved treatment options.

The research activities will deliver comprehensive characterization of sarcomere structure and function alterations caused by specific C2 domain mutations, utilizing advanced molecular and physiological analysis techniques. By clarifying the pathophysiological mechanisms underlying DA through controlled experimental models and mechanistic investigations, the project aims to generate foundational knowledge that will support the development of targeted therapeutic interventions and improve clinical outcomes for DA patients currently limited to physical therapy approaches with limited efficacy.