Duchenne muscular dystrophy is a rare, X-linked recessive disease caused by the loss of functional dystrophin resulting in progressive, severe skeletal myopathy and cardiomyopathy, which is the leading cause of death. Overt cardiomyopathy typically manifests late in the second decade. However, intermittent and asymptomatic troponin I elevations and subtle declines in systolic function can be observed before the age of 10. This underscores the urgent need for therapies that not only restore dystrophin in skeletal muscle but also to target the heart to preserve cardiac function.
AAV-SLB101, Solid Biosciences’ proprietary capsid, was rationally designed to improve cardiac and skeletal muscle tropism and is utilized in SGT-003, Solid’s next-generation, investigational microdystrophin gene therapy for Duchenne. AAV-SLB101 demonstrated increased muscle tropism and decreased liver uptake in both healthy animals and disease models (wild type and mdx mice, non-human primates, and human myotubes and iPSC-derived cardiac myocytes) when compared to first generation vectors (AAV9 and AAVrh74). In the mdx mouse model of Duchenne and in non-human primates, AAV-SLB101-mediated transgene expression was several-fold higher than AAVrh74 in multiple muscle groups, and specifically four times higher in the heart.
Early findings in the Phase 1/2 INSPIRE DUCHENNE (NCT06138639) study investigating SGT-003 indicate a positive safety profile, high levels of microdystrophin expression, and potentially favorable changes in cardiac biomarkers as of a data cutoff of December 15, 2025. In participants with increased troponin I at baseline, levels have been reduced post-treatment and improvements in systolic function have also been observed. These findings suggest that SGT-003 may not only slow skeletal muscle decline but may also mitigate the progressive cardiomyopathy that has increasingly becoming a leading cause of death for patients with Duchenne.
Together, these findings underscore the potential for AAV-SLB101 as a targeted gene therapy vector for neuromuscular and cardiac indications, such as Duchenne.