A Phase I/II, open-label, dose escalation study to evaluate the safety of 2 doses of intravenous ATA-200, an adeno-associated viral vector carrying the human gamma-sarcoglycan gene, in patients with gamma-sarcoglycanopathy (limb-girdle muscular dystrophy LGMDR5, formerly LGMD2C).

limb-girdle muscular dystrophy type R5 (previously named LGMD2C)

incidence of AEs recording throughout the study, incidence of clinically relevant abnormalities detection in vital signs, physical examination findings, vital signs, myalgia assessment, cardiac assessment, laboratory determinations

Efficacy: muscle Function Tests: North Star Assessment for Neuromuscular Disorders (NSAD) and Performance of the Upper Limb (PUL), Efficacy: timed Function Tests: 10-meter walk test (10MWT); 100-Meter Walk Test (100MWT); Time to Rise From Floor (RFF); 4-Stair climb test, Efficacy: muscle Strength Tests: Myotools and Hand Held Dynamometry (HHD), Efficacy: Imaging Assessments: Muscle Nuclear Magnetic Resonance Imaging (NMRI) and spectroscopy: quantitative NMRI (including fat-water separation, based MRI and NMRS) in the lower limbs, Efficacy: Respiratory assessments: Pulmonary function tests, including forced vital capacity (FVC), minimal inspiratory/expiratory pressure (MIP/MEP), sniff nasal inspiratory pressure (SNIP) test, Efficacy: Respiratory assessments: Respiratory questionnaire, Efficacy: Muscle Biopsy: Histological assessment, including centronucleation index and fibrosis assessment, Efficacy: Muscle Biopsy: VCN: quantification of vector copy number per diploid cell, Efficacy: Muscle Biopsy: SGCG transgene expression (at protein and mRNA levels), Efficacy: Muscle Biopsy: Quantification of human sarcolemmal SGCG-positive fibers by immunohistochemistry, Efficacy: Muscle Biopsy: Quantification of human alpha-sarcoglycan positive fibers by immunohistochemistry, Efficacy: Muscle Biopsy: Exploratory biomarkers, e.g., TMEM8 for regeneration, FN1 for fibrosis, and CD11b for inflammation, microRNA, Efficacy: Patient reported outcome and QoL: Fatigue Visual Analog Scale (VAS), Efficacy: Patient reported outcome and QoL: EQ-5D-Y and EQ-5D-Y proxy 1 questionnaires (based on patient age), Efficacy: Patient reported outcome and QoL: Daily activity living (ACTIVLIM neuromuscular scale), Efficacy: Patient reported outcome and QoL: Change in video outcomes capturing disease hallmarks, Efficacy: Biomarkers: Creatine kinase (CK), myomesin-3, circulating microRNA, Efficacy: Biomarkers: Blood and urine biobanking

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