Identifying and Evaluating Treatments for Duchenne Muscular Dystrophy and Other Muscle Disorders

Technology Overview

Dr. Lisa Maves

The debilitating neuromuscular disorder known as Duchenne muscular dystrophy (DMD) is caused by genetic mutations that result in the loss of a functional dystrophin protein. Dystrophin connects the interior of a muscle fiber to its extracellular matrix and is essential for stabilizing muscle cells when they contract. DMD is marked by progressive muscle weakness and degeneration that eventually leads to the failure of muscles involved in movement, breathing and cardiac function. Patients with DMD usually succumb to heart failure, and there is no known cure for the disease.

Developmental biologist Lisa Maves, PhD, has led research efforts with a zebrafish model of DMD and is using this preclinical model system to understand underlying disease mechanisms and to screen for new therapeutic compounds. The Maves Lab has used novel chemical screening approaches to identify new small molecules that improve DMD in zebrafish.

From a chemical library screen of more than 800 small molecules, Dr. Maves and her team have identified a promising molecule called SR-4370, a histone deacetylase inhibitor (HDACi). SR-4370 significantly reduced muscle degeneration and extended longevity in zebrafish with a dmd gene mutation. The potential therapeutic SR-4370 is related to another HDACi called givinostat, which was approved by the U.S. Food and Drug Administration in 2024 for treating patients who have DMD. In human DMD clinical trials, givinostat is the only nonsteroidal small molecule that has shown a functional, albeit minimal, benefit in delaying disease progression. Thus, HDACi represents a promising new drug class for DMD.

Studies in the Maves Lab show that SR-4370 is significantly more effective than givinostat in improving DMD disease in zebrafish. Based on these promising results, Dr. Maves is forming collaborations to conduct more preclinical testing and safety trials of SR-4370 in other animal models, with an eventual goal of human clinical trials. This method of use represents a technology asset available for licensing and co-development.

In addition to SR-4370 and HDACi, Dr. Maves is interested in using the zebrafish model to assess other potential DMD drug therapies. Zebrafish offer several key advantages for initial preclinical work:

• Drug efficacy can be established in a few days.
• Drug combinations can easily be tested side-by-side.
• They have a closer resemblance to human DMD in symptom severity than seen in other animal models.
• Cardiac and skeletal muscle phenotypes can easily be monitored for information on structure and function, respectively.
• Biomarkers can easily be monitored.

The zebrafish platform can be used for comparative testing of small molecules (including chemical modifications of existing small molecule drugs), understanding drug biochemistry, and clarifying downstream mechanisms. Analyses of the DMD zebrafish cardiac phenotype and cardiac mRNA markers can address a key knowledge gap in DMD cardiac issues that are relevant for developing new therapies. Biochemical target assays can reveal if known targets of small molecules have been affected and how they correlate with outcomes in dmd zebrafish. The platform can also be used to assess mRNA and microRNA biomarkers associated with disease progression and drug-induced disease amelioration, using qRT-PCR and RNA-seq. In addition, the Maves Lab is developing novel fluorescently tagged dmd zebrafish alleles to facilitate early disease and high-throughput studies.

Dr. Maves has considerable expertise in zebrafish models of DMD and other diseases, in CRISPR gene engineering to create precise genetic mutations, and in refining and performing a range of drug-evaluation tests such as biochemical target assays and heart function assays to assess the benefit of candidate drugs or their potential cardiotoxicity. The aquatics facility at Seattle Children’s Research Institute is well-equipped with specific tools for measuring muscle abnormality in the zebrafish DMD model and is well-suited for rapid, high-throughput screening of therapies, either individually or in combination. The Maves Lab also has the expertise to engineer new zebrafish models for other muscle disorders.

Dr. Maves is interested in partnerships not only for developing the SR-4370 histone deacetylase inhibitor as a potential DMD therapeutic but also for using her zebrafish platform to explore other disease pathways and test additional DMD drug candidates. Her research tools likewise can be applied to facioscapulohumeral muscular dystrophy (FSHD) and other muscle disorders.

Stage of Development

• Pre-clinical in vivo

Partnering Opportunities

• Collaborative research opportunity
• Sponsored research agreement
• Technology Licensing
• Consultation agreement
• Clinical trials
• Animal model access
• High-throughput screening

Learn More

• Lisa Maves, PhD
• Maves Lab
• Developmental Disease Modeling, Gene Discovery, and Drug Screening

Publications

1. Ke’ale WL, Hasegawa EH, Farr GH III … Maves L. Epigenetic small molecule screening identifies a new HDACi compound for ameliorating Duchenne muscular dystrophy. Mol Ther Nucleic Acids. 2025;36(3):102683.
2. Barrett P, Louie KA, Dupont JB, Mack DL, Maves L. Uncovering the embryonic origins of Duchenne muscular dystrophy. WIREs Mech Dis. 2024;16(6):e1653.
3. Karuppasamy M, English KG, Henry CA … Maves L. Standardization of zebrafish drug testing parameters for muscle diseases. Dis Model Mech. 2024;17(1):dmm050339.
4. Farr GH III, Morris M, Gomez A … Maves L. A novel chemical-combination screen in zebrafish identifies epigenetic small molecule candidates for the treatment of Duchenne muscular dystrophy. Skelet Muscle. 2020;10(1):29.
5. Talbot J, Maves L. Skeletal muscle fiber type: using insights from muscle developmental biology to dissect targets for susceptibility and resistance to muscle disease. Wiley Interdiscip Rev Dev Biol. 2016;5(4):518-534.
6. Maves L. Recent advances using zebrafish animal models for muscle disease drug discovery. Expert Opin Drug Discov. 2014;9(9):1033-1045.
7. Johnson NM, Farr GH III, Maves L. The HDAC inhibitor TSA ameliorates a zebrafish model of Duchenne muscular dystrophy. PLOS Curr. 2013;5:ecurrents.md.8273cf41db10e2d15dd3ab827cb4b027

Last updated 6/15/2026