Stem Cell Rev Rep. 2025 Dec 18. doi: 10.1007/s12015-025-11039-8. Online ahead of print.
ABSTRACT
Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle degeneration and premature mortality. This study evaluated the long-term safety and efficacy of DT-DEC01, a Dystrophin Expressing Chimeric (DEC) cell therapy, in non-ambulatory DMD patients following systemic intraosseous administration. Three non-ambulatory DMD patients aged 11 to 16 years, each carrying a different DMD mutation (deletion of exons 48-50, deletion of exon 52, or nonsense mutation), received DT-DEC01 at doses of 2 × 10⁶, 4 × 10⁶, and 6 × 10⁶ cells/kg, respectively, without immunosuppression. Safety assessment included monitoring of Adverse Events (AE), Serious Adverse Events (SAE), and Donor-Specific anti-HLA Antibodies (DSA). Efficacy evaluations included Performance of Upper Limb (PUL 2.0) test, grip strength, electromyography (EMG)-assessed Motor Unit Potential (MUP) duration, echocardiography, spirometry, and wristband-based arm movement quantification. No treatment-related AE, SAE, or DSA were detected through 24 months of follow-up. All three patients demonstrated measurable and sustained improvements across multiple functional domains following systemic DT-DEC01 administration. Patient-specific gains included improved cardiac parameters, prolonged MUP duration, enhanced respiratory capacity, and increased upper-limb strength. Notably, these improvements occurred in non-ambulatory patients - a disease stage typically associated with progressive cardiac and pulmonary decline, rather than functional recovery. These sustained functional benefits up to 24 months suggest that DT-DEC01 therapy may promote multisystem functional improvements in advanced DMD, independent of dystrophin mutation type or disease stage.
PMID:41410800 | DOI:10.1007/s12015-025-11039-8