Federal Project Grant Award Summary

Baylor College of Medicine received a $679,931 Project Grant award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846), effective April 20, 2026, with a completion date of March 31, 2031. The research investigates the role of SPEG-regulated sarcoplasmic reticulum calcium leak in muscle function and disease pathophysiology, focusing on excitation-contraction coupling (ECC) proteins and their relationship to congenital myopathies. The project will elucidate mechanisms by which the SPEG kinase regulates calcium leak through the RYR1 calcium release channel via phosphorylation at serine 2902, and will assess whether this phosphorylation site modification improves muscle and mitochondrial function in myopathy models and mitigates age-related muscle decline.

The research deliverables include mechanistic characterization of SPEG kinase domain function, evaluation of the S2902D phosphomimetic mutation's effects on muscle performance across multiple myopathy models, and assessment of a therapeutic compound (S107) for off-target effects and efficacy in treating calcium leak-initiated versus triad disruption-initiated myopathies. The project will generate preclinical data on novel therapeutic targets for muscle disorders characterized by abnormal sarcoplasmic reticulum calcium handling, contributing to the NIAMS program's objectives of advancing understanding of musculoskeletal disease mechanisms and developing innovative treatment approaches.