Adeno-associated virus vector delivery of β-sarcoglycan and the treatment of muscular dystrophy
AssigneeResearch Institute At Nationwide Children's Hospital
InventorsLouise Rodino-Klapac, Jerry R. Mendell
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Abstract
Described herein are methods of treating muscular dystrophy comprising administering a recombinant AAV (rAAV) scAAVrh74.MHCK7.hSGCB vector, methods of expressing beta-sarcoglycan gene in a patient, pharmaceutical compositions comprising the rAAV, and methods of generating the rAAV. The disclosed methods reduce fibrosis and improve muscle function by restoring B-sarcoglycan expression in muscle tissues. The disclosure further provides preclinical studies in animal models, and a clinical trial involving systemic delivery of the vector to patients, which shows significant improvements in muscle pathology, force production, and overall activity in treated subjects.
Claims10
A method of treating limb-girdle muscular dystrophy Type 2E (“LGMD2E”) in a subject in need thereof, comprising the step of administering a recombinant adeno-associated virus (rAAV) which comprises SEQ ID NO:
- 19 to the subject, wherein
- the rAAV is administered using a systemic route of administration and at a dose of a) about 1.85×1013 vg/kg or about 7.41×1013 vg/kg based on a linearized plasmid as the quantitation standard, or b) about 1.0×1013 vg/kg or about 5.0×1014 vg/kg based on a supercoiled plasmid as the quantitation standard.
A method of treating limb-girdle muscular dystrophy Type 2E (“LGMD2E”) in a subject in need thereof, comprising the step of administering a recombinant adeno-associated virus (rAAV) which comprises SEQ ID NO:
- 19 to the subject,
- wherein administration of the rAAV decreases the serum creatine kinase (CK) level in the subject as compared to the serum CK level before the administration of the rAAV.
A method of treating limb-girdle muscular dystrophy Type 2E in a subject in need, comprising administering to the subject an intravenous infusion of an rAAV construct over approximately 1 to 2 hours at a dose of about 5.0×1013 vg/kg or about 2.0×1014 vg/kg based on a supercoiled plasmid as the quantitation standard, or about 1.85×1013 vg/kg or 7.41×1013 vg/kg based on a linearized plasmid as the quantitation standard, and wherein the rAAV construct comprises SEQ ID NO:
- 19.
A method of increasing localization of alpha-sarcoglycan to a cell membrane in a subject in need thereof comprising administering to the subject a recombinant adeno-associated virus (rAAV) construct which comprises SEQ ID NO:
- 19.
Dependencies are inferred from the claim text.