Systemic gene replacement therapy for treatment of X-linked myotubular myopathy (XLMTM)
AssigneesWake Forest University Health Sciences Genethon, Children's Medical Center Corporation
InventorsMartin K. Childers, Alan H. Beggs, Ana Maria Buj Bello
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Abstract
The present invention provides compositions and methods for treating a myopathy. In certain embodiments, the invention provides compositions and methods for treating, improving muscle function, and prolonging survival in a subject with X-linked myotubular myopathy (XLMTM). The present invention provides a method comprising systemic administration of a composition that induces the increased expression of myotubularin in the muscle of a subject. The invention provides sustained regional and global increases in muscle function.
Claims10
A method of making a Myotubularin 1 recombinant viral vector (rViral-MTM1) for treating an X-linked myotubular myopathy (XLMTM) in a mammal in need thereof, the method comprising:
- a. generating a first recombinant baculovirus comprising a viral rep gene and a viral cap gene;
- b. generating a second recombinant baculovirus comprising an insert that comprises an MTM1 cDNA cloned downstream of a muscle specific promoter wherein the insert is flanked by viral inverted terminal repeats (ITRs), and;
- c. infecting a cell with the first and second recombinant baculoviruses, wherein when the first and second recombinant baculoviruses are expressed in the cell, rViral-MTM1 vector particles are generated;
- wherein the viral vector, the viral rep gene, the viral cap gene, and the viral ITR are from an adeno-associated virus (AAV);
- and
- wherein AAV comprises a serotype selected from the group consisting of AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, and AAV9.
A method of making a Myotubularin 1 recombinant viral vector (rViral-MTM1) for treating an X-linked myotubular myopathy (XLMTM) in a mammal in need thereof, the method comprising:
- a. generating a first expression plasmid comprising a viral rep gene and a viral cap gene;
- b. generating a second expression plasmid comprising an insert that comprises an MTM1 cDNA cloned downstream of a muscle specific promoter wherein the insert is flanked by viral inverted terminal repeats (ITRs), and;
- d. transfecting a cell with the first and second expression plasmids and with a third viral helper plasmid, wherein when the first and second plasmids are expressed in the cell, rViral-MTM1 vector particles are generated;
- wherein the viral vector, the viral rep gene, the viral cap gene, and the viral ITR are from an adeno-associated virus (AAV);
- and
- wherein AAV comprises a serotype selected from the group consisting of AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, and AAV9.
Dependencies are inferred from the claim text.