Axonopathy in Duchenne Muscular Dystrophy limits microdystrophin gene therapy efficacy

Advancing adeno-associated virus (AAV) gene therapy for Duchenne muscular dystrophy

A human skeletal muscle xenograft model is adapted, using 222 transplanted muscles from human donors, to use as a platform for AAV delivery and shows for the first time, that human muscles transplanted in immune-deficient mice are efficiently transduced by AAV vectors at following intravenous injection of the host mice...

KLHL40 gene replacement therapy in severe nemaline myopathy improves survival and skeletal muscle function in a preclinical mouse model

Early loss of axons limits the therapeutic window in a mouse model of spinal muscular atrophy

Current treatments for spinal muscular atrophy have significantly improved patient prognosis, but still fall short of a full cure, particularly when administered after symptom onset. To improve future therapies, it is essential to identify the early pathological events that currently limit treatment efficacy. Here we...

RNA trans-splicing treatment for Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a fatal disorder caused by dystrophin mutations, leading to progressive muscle degeneration and cardiac failure. Although AAV-based DMD therapies with innovative designs to overcome the cargo limits of the virus are effective in animal models, these current systems may face clinical...

Regeneration-associated utrophin expression in skeletal muscle: implications for utrophin-targeted therapies

Duchenne muscular dystrophy (DMD) is a lethal, X-linked muscle-wasting disease caused by loss of dystrophin. Utrophin, a structural and functional paralogue of dystrophin, can compensate for dystrophin deficiency and represents a therapeutic target applicable to patients irrespective of their DMD mutation. However, utr...

Novel Therapeutic Frontiers in Duchenne Muscular Dystrophy: Gene Therapy, Exon Skipping, and Stem Cell Approaches.

Through multidisciplinary treatment and continuous scientific progress, individualized precision medicine that integrates therapies targeting secondary pathogenic pathways with dystrophin-restoration techniques can finally convert this devastating illness into a tolerable chronic ailment.