A rare and devastating genetic disease, Duchenne muscular dystrophy (DMD) causes progressive muscle loss due to the absence of dystrophin, a structural and functional protein that protects muscle fibers during everyday movement. Without dystrophin, muscle tissue is highly susceptible to damage and gradually weakens over time.
As the disease progresses, patients lose mobility, develop respiratory complications and often face a shortened life expectancy. Although newer therapies have improved clinical care, they do not fully prevent ongoing muscle injury or disease progression.
Supported by a three-year, $300,000 research grant from the Muscular Dystrophy Association (MDA), Anirban Roy, Ph.D., research assistant professor in the Department of Pharmacological and Pharmaceutical Sciences, is leading a study aimed at identifying novel molecular targets that drive muscle degeneration in DMD.
The research focuses on Transforming Growth Factor-β–Activated Kinase 1 (TAK1), a signaling protein known to regulate inflammation, muscle growth and cell survival. Work conducted in the laboratory of Ashok Kumar, Else and Philip Hargrove Endowed Professor of Drug Discovery, demonstrated that TAK1 is essential for maintaining healthy muscle. However, in Duchenne muscular dystrophy, TAK1 becomes abnormally activated early in disease progression and contributes to muscle fiber death, chronic inflammation and tissue scarring.
Using a well-established mouse model of Duchenne muscular dystrophy, the research team found that transient inhibition of TAK1 during early disease stages reduced muscle damage and inflammatory signaling, while preservation of TAK1 activity at later stages was necessary to maintain muscle mass and strength.
Building on these findings, the MDA-funded project will apply advanced genetic, biochemical and proteomic approaches to define TAK1-dependent mechanisms driving muscle degeneration and fibrosis in DMD. The study will also evaluate small-molecule TAK1 inhibitors in preclinical models to assess their therapeutic potential, including compatibility with existing DMD treatments.
“By identifying specific, druggable pathways that limit muscle damage while preserving muscle integrity, this research aims to advance therapeutic strategies that improve mobility, daily function and long-term outcomes for individuals living with Duchenne muscular dystrophy,” Roy said.