ABS 032: Investigation of Chronodisruption in Duchenne Muscular Dystrophy Patients and Mice

Yashodhara Velayudam ¹, Miguel A. Monreal-Gutierrez ⁵, Katherine G. English ¹, Muthukumar Karuppasamy ¹, Shelby Rorrer ¹, Michael A. Lopez ¹, Jodi Paul ⁸, Han C. Phan ¹ ⁷, Karen L. Gamble ⁸, Karyn A. Esser ⁵ ⁶, Matthew S. Alexander ¹-⁴

¹ Department of Pediatrics, Division of Neurology at Children’s of Alabama and the University of Alabama at Birmingham, Birmingham, AL
² UAB Center for Exercise Medicine (UCEM), Birmingham, AL
³ Department of Genetics, University of Alabama at Birmingham, Birmingham, AL
⁴ UAB Civitan International Research Center (CIRC), Birmingham, AL
⁵ Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL
⁶ Myology Institute, University of Florida, Gainesville, FL
⁷ Rare Disease Research, LLC, Atlanta, GA
⁸ Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL

The Van Wickle Journal (2026) Volume 2, ABS032

Introduction: Duchenne muscular dystrophy (DMD) is a progressive, X-linked neuromuscular disorder, caused by a pathogenic variant in the DMD gene, resulting in dysfunctional DYSTROPHIN protein, muscle atrophy, cardiomyopathy, and respiratory failure. Chronodisruption refers to the chronic disruption of the body’s circadian rhythm that is moderated through transcription of thousands of CLOCK-controlled genes. These genes regulate muscle function and mitochondrial metabolism, which are both severely disrupted in DMD-affected tissues and organs. While dystrophin loss causes DMD, circadian rhythms also affect muscle health, and their disruption corresponds to negative DMD patient outcomes.

Methods: To study circadian disruption in DMD, the expression of circadian rhythm genes and the circadian transcriptome in wildtype and mdx (DMD) mice were analyzed. Diurnal behavior analysis was also performed to study activity during light phase and onset, which was quantified by a periodogram power score. In parallel DMD patient studies, we used wrist wearable actigraphy monitors to measure activity and chronicity in DMD ambulatory and non-ambulatory patients of mixed aged cohorts.

Results: Mdx mice exhibited increased activity onset, phase shift of activity onset, increased activity in subjective night, and significantly less robust rhythmic behavior. In DMD patients, significant sleep disruption, decreased sleep duration, as well as poor sleep efficiency were observed over a two-week interval in correlation with age and dystrophic disease progression.

Discussion: Overall, DMD mice have progressively disrupted circadian rhythms. Our findings provide initial evidence for investigating a novel role of dystrophin in disrupting the circadian rhythm in DMD mice and patients. Further experimentation through RNA-sequencing and Dmd conditional knockout (KO) mice may provide insight into how circadian rhythm impacts DMD progression.