Muscle Regeneration and Therapeutic Strategies in Muscular Dystrophy

Muscular dystrophies encompass a group of inherited disorders characterised by progressive loss of muscle fibre integrity, chronic inflammation, aberrant repair and eventual replacement of functional tissue with fibrotic scar. Central to the intrinsic repair capacity of skeletal muscle are satellite cells, a quiescent stem cell population that activates, proliferates and differentiates to replace damaged myofibres. In dystrophic muscle, repeated cycles of degeneration exhaust the satellite cell pool, while the persistent inflammatory milieu and deposition of extracellular matrix impede effective regeneration and promote fibrosis. Understanding the interplay between muscle stem cells, immune cells and the extracellular environment is essential for the design of interventions that restore function and delay disease progression.

Therapeutic approaches span genetic, cellular and biomaterial strategies. Genetic therapies aim to correct or bypass mutations in the dystrophin gene by exon skipping, gene replacement or targeted gene editing. Cell therapies seek to augment or replenish the satellite cell compartment, while biomaterial scaffolds and small-molecule modulators of myostatin, inflammation or fibrosis offer complementary routes to enhance tissue repair. Recent advances in high-resolution profiling of muscle composition and digital phenotyping of disease trajectories underpin the development of personalised interventions and outcome measures.

Research from Nature Portfolio

Single-cell and single-nucleus transcriptomic and chromatin accessibility mapping across adult human skeletal muscle have delineated changes in stem, immune and stromal cell populations with age and frailty, identifying epigenetic features that correlate with regenerative decline and potential molecular targets for intervention. Wearable sensor technology combined with machine learning has yielded a digital biomarker capable of distinguishing Duchenne muscular dystrophy patients from controls and predicting disease progression, offering a sensitive, non-invasive tool to monitor therapeutic responses in clinical trials.

Muscle Regeneration and Therapeutic Strategies in Muscular Dystrophy publication trend

The graph below shows the total number of articles in muscle regeneration and therapeutic strategies in muscular dystrophy across all publications each year (not limited to Nature Index journals).

Technical terms

Satellite cell: A muscle-resident stem cell that activates upon injury to proliferate and repair damaged fibres.

Fibrosis: Pathological deposition of extracellular matrix that replaces functional muscle tissue and impedes regeneration.

Exon skipping: An antisense oligonucleotide-based approach to modulate pre-mRNA splicing and restore the reading frame of mutated genes.

Antisense oligonucleotide: A short synthetic nucleic acid designed to bind RNA and alter splicing or translation.

Biomaterial scaffold: A synthetic or natural matrix that supports cell attachment, proliferation and tissue regeneration.

Transcriptomics: The study of the complete set of RNA transcripts to profile gene expression in cells or tissues.

References

1. Aberrant repair and fibrosis development in skeletal muscle. Skeletal Muscle (2011).
2. Intrinsic and extrinsic mechanisms regulating satellite cell function. Development (2015).
3. Multimodal cell atlas of the ageing human skeletal muscle. Nature (2024).
4. Wearable full-body motion tracking of activities of daily living predicts disease trajectory in Duchenne muscular dystrophy. Nature Medicine (2023).
5. Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss. Nano-Micro Letters (2024).
6. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle & Nerve (2014).
7. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy. Disease Models & Mechanisms (2015).