Limb girdle muscular dystrophy (LGMD), type 2C (gamma-sarcoglycanopathy) Musculoskeletal Diseases Limb girdle muscular dystrophy (LGMD), type 2C (gamma-sarcoglycanopathy)
Conditions
Interventions
1. No placebo arm
2. Six month follow-up on AAV1 ? ?-sarcoglycan, AAV1 replication-defective vector expressing the human ?-sarcoglycan gene under the control of the desmin promoter, prepared for clini
Sponsors
Genethon (France)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Confirmed diagnosis of LGMD 2C including: 1.1. Molecular analysis proving del525T mutation on ?-sarcoglycan gene (chromosome 13) at homozygous state 1.2. Muscle biopsy with immunohistochemical and/or Western blot analysis showing marked decrease or absence of ?-sarcoglycan staining in muscle, as well as a fibrosis assessment should be available. If not, an initial muscular biopsy may be performed during the pre-enrolment period 2. Minimum age of 15 years 3. Males and females may be equally enrolled 4. Adequate carpi radialis muscle bulk for muscle biopsy as assessed by examination 5. Subjects should be able to communicate with the investigation staff 6. Subjects should be able to understand, to comply with and to perform all needed evaluations during the trial period including muscle strength tests 7. Forearm muscle strength should be of at least 3+ as assessed through the British Medical Research Council (MRC) Manual Muscle Testing (MMT) scale 8. Subjects should also have already lost ambulation 9. Subjects should be able and willing to return for follow up 10. Subjects should be able and willing to give signed informed consent 11. For minor subjects, a signed informed consent will be given by a legally authorised representative 12. Eligible subjects belonging to a multiplex family should not be enrolled in the same cohort
Exclusion criteria
Exclusion criteria: 1. Severity of disease and presence of ill-prognosis complications: 1.1. Severe respiratory dysfunction such as subjects with tracheostomy or forced vital capacity (FVC) 10 mg/l (> 17 µmol/l) 2.4. Serum creatinine > 110 µmol/l 2.5. Lymphocytes CD4+ < 250/mm3 (< 15%) 2.6. History of diabetes mellitus 2.7. Current infectious diseases, including known positive human immunodeficiency virus (HIV) serology, hepatitis B and C 2.8. Abnormal profile on protein immunoelectrophoresis 2.9. Immunisations of any kind within the past month 2.10. Receipt of another investigational agent within 4 weeks of study enrolment 2.11. History of or current steroid medication for indications other than muscular dystrophy, chemotherapy, radiotherapy or other immunosuppressive therapy 2.12. Steroid medication, if any, should be discontinued at least 3 months before entering the protocol and not received during the study 2.13. Pregnant or lactating women 2.14. 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 2.15. Pre-injection neutralising anti-AAV1 antibodies titer (on pre-enrolment / D-30 visit) superior or equal to 1/800
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assessment of clinical tolerance by standard clinical examination | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Assessment of biological, immunological, histological and functional tolerance by laboratory monitoring, evaluation of humoral and cellular immune response to both transgene and vector as well as non-specific immune response, evaluation of histological changes on muscle biopsy and evaluation of changes in muscle function 2. Assessment of efficacy through studies of transduction efficiency, distribution, expression and fiber type specificity and muscle biopsy histological changes (based on immunohistochemistry and Western blot studies and analysis of sarcoglycan labelling) | — |
Countries
France
Outcome results
None listed