Project Grant R21AR087779

The National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded the University of Arizona $375,381 on September 2, 2026, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846) to develop a small-molecule drug discovery platform targeting MYBPC1 mutations that cause distal arthrogryposis.

The project addresses the absence of available therapeutics for distal arthrogryposis, a congenital muscle disorder affecting approximately 1 in 3,000 live births and characterized by joint contractures, muscle weakness, and reduced mobility. The University of Arizona will use fluorescence lifetime-based high-throughput screening tools to identify small-molecule compounds that bind to normal and mutant slow skeletal myosin binding protein-C (SMYBP-C) N-terminal domains. The work integrates machine learning-based virtual screening for hit-to-lead optimization and will evaluate promising drug candidates using in vitro biochemical and biophysical assays, in silico molecular dynamics simulations, and testing in newly characterized MYBPC1 knock-in mouse models carrying human distal arthrogryposis mutations.

Performance of performance is Tucson, Arizona. The award runs through August 31, 2028, under the Project Grant assistance type.