Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy

Figures

• 

  Figure 1.. Study Flow Diagram

• 

  Figure 2.. Lack of Vector-Associated Toxic Effects by Histopathological Assessments in 4 Patients A, Hematoxylin-eosin staining (original magnification ×20) shows unremarkable alterations in central nucleation (yellow arrowheads) of muscle fibers before and after treatment. Baseline (pretreatment) biopsy results show levels of necrosis (white arrowheads), stages of degeneration or regeneration, and increased connective tissue (black arrowheads). B, Picrosirius red staining shows a reduction in fibrosis after treatment. C, Fibrosis in tissue samples was measured by the percentage of collagen accumulation in tissue section. The error bars refer to the SD.

• 

  Figure 3.. Systemic Administration of rAAVrh74.MHCK7.micro-dystrophin A, Frozen biopsied tissue sections of the gastrocnemius muscle were processed and stained with DYS3 antibody to detect micro-dystrophin. B, Micro-dystrophin compared with full-length protein was seen in 4 patients with Duchenne muscular dystrophy (DMD) before and after treatment (day 90) with rAAVrh74.MHCK7.micro-dystrophin. α-Actinin was used as a loading control, and sample from a patient was included as a negative control. NC indicates normal control. aPatient 4 had a positive immunoreactive band that was above the upper limit of quantification and was diluted 1 to 4 before loading in the representative gel.