dystrophinsparing

Dystrophin sparing refers to therapeutic strategies aimed at preserving or restoring the function of dystrophin, a critical protein for maintaining muscle cell integrity. Dystrophin links the cytoskeleton of muscle fibers to the surrounding extracellular matrix, and its deficiency underlies Duchenne and Becker muscular dystrophies. Rather than compromising the protein, dystrophin-sparing approaches seek to rescue or sustain its levels.

One major technique is exon-skipping therapy using antisense oligonucleotides that modulate pre‑mRNA splicing, enabling the production of internally truncated but still functional dystrophin. Several clinical trials have demonstrated partial dystrophin restoration and slowed progression of muscle weakness. Small molecules that upregulate dystrophin or enhance its stability are also being investigated, as are approaches that target the dystrophin gene enhancer elements to boost transcription.

Gene editing platforms, particularly CRISPR/Cas9 systems, are increasingly explored. These tools can repair mutations in situ or re‑configure the dystrophin gene to reconstitute a viable protein. Viral vector‑mediated delivery of donor templates or double‑cut systems allows precise insertion or restoration, potentially offering lasting dystrophin expression.

Emerging research also considers the role of post‑translational modifications and protein‑processing pathways. Inhibiting proteases or chaperone‑mediated degradation could reduce dystrophin loss in damaged fibers. Integration of these strategies with conventional physiotherapy and pharmacologic interventions is expected to enhance patient outcomes.

Future developments focus on improving delivery efficiency, minimizing immune responses, and ensuring long‑term safety. If successful, dystrophin-sparing therapies could shift the treatment paradigm from symptomatic management to true disease modification, providing sustained muscle function for patients with dystrophinopathies.