Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C

Exclusion Criteria

• •1. Severity of disease and presence of ill-prognosis complications:
• •* Severe respiratory dysfunction such as subjects with tracheostomy or forced vital capacity (FVC) \< 1000 ml and/or \< 30%;
• •* Uncompensated heart failure;
• •* An ejection fraction (EF) \< 30% as measured on either echocardiography or scintigraphy;
• •* Severe rhythm disturbances and/or high degree conduction defect in the absence of a pacemaker insertion.
• •2. Underlying conditions, diseases or active viral infections likely to increase risk of complications or to interfere with the investigational treatment:
• •* contraindications for injections and muscle biopsies
• •* Platelet count \< 100,000 / mm3
• •* Total bilirubin \> 10 mg/l (\> 17 µmol/l)
• •* Serum creatinin \> 110 µmol/l
• •* Lymphocytes CD4+ \< 250/mm3 (\< 15%)
• •* History of diabetes mellitus
• •* Current infectious diseases, including known positive HIV serology, hepatitis B and C
• •* Abnormal profile on protein immunoelectrophoresis
• •* Immunizations of any kind within the past month
• •* receipt of another investigational agent within 4 weeks of study enrollment
• •* History of or current steroid medication for indications other than muscular dystrophy, chemotherapy, radiotherapy or other immunosuppressive therapy. Steroid medication, if any, should be discontinued at least 3 months before entering the protocol and not received during the study
• •* Pregnant or lactating women. Females or males of childbearing age must be willing to employ adequate contraception, that is to use condoms during the 3 months following the administration of the product
• •* Pre-injection neutralizing anti-AAV1 antibodies titer (on pre-enrollment / D-30 visit) superior or equal to 1/800.