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
Life of this patent
Estimating the term…
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.
Claims34
A method of treating an X-linked myotubular myopathy (XLMTM) in a mammal in need thereof, the method comprising administering intramuscularly to the mammal a composition that increases expression of myotubularin in a muscle of the mammal, wherein the composition comprises an adeno-associated viral (AAV) vector comprising a nucleic acid sequence encoding the myotubularin gene (MTM 1) operably linked to a muscle specific promoter, further wherein the function of the diaphragm of the mammal is improved, as compared to the diaphragm of the mammal in the absence of administration of the composition, wherein strength is increased in the muscle.
A method of prolonging the survival of a mammal with an X-linked myotubular myopathy (XLMTM), the method comprising administering intramuscularly to the mammal a composition that increases expression of myotubularin in a muscle of the mammal, wherein the composition comprises an adeno-associated viral (AAV) vector comprising a nucleic acid sequence encoding the myotubularin gene (MTM 1) operably linked to a muscle specific promoter, further wherein the function of the diaphragm of the mammal is improved, as compared to the diaphragm of the mammal in the absence of administration of the composition, wherein strength is increased in the muscle, and wherein survival of the mammal is prolonged.
A method of treating an X-linked myotubular myopathy (XLMTM) in a mammal in need thereof, the method comprising administering intramuscularly to the mammal a composition that increases the expression of myotubularin in a muscle of the mammal, wherein the composition comprises a viral vector comprising a nucleic acid sequence encoding an Myotubularin 1 (MTM1) gene operably linked to a muscle specific promoter and wherein the muscle of the mammal administered the composition exhibits an increase in MTM1 expression for a period selected from the group consisting of up to 3 months, up to 6 months and up to 1 year, as compared with the muscle of a mammal not administered the composition.
A method of prolonging the survival of a mammal with an X-linked myotubular myopathy (XLMTM), the method comprising administering intramuscularly to the mammal a composition that increases the expression of myotubularin in a muscle of the mammal, wherein the composition comprises a viral vector comprising a nucleic acid sequence encoding an Myotubularin 1 (MTM1) gene operably linked to a muscle specific promoter and wherein the muscle of the mammal administered the composition exhibits an increase in MTM1 expression for a period selected from the group consisting of up to 3 months, up to 6 months and up to 1 year, as compared with the muscle of a mammal not administered the composition.
A method of restoring normal muscle function in a mammal with an X-linked myotubular myopathy (XLMTM), the method comprising administering intramuscularly to the mammal a composition that increases the expression of myotubularin in a muscle of the mammal, wherein the composition comprises a viral vector comprising a nucleic acid sequence encoding an Myotubularin 1 (MTM1) gene operably linked to a muscle specific promoter and wherein the muscle of the mammal administered the composition exhibits an increase in MTM1 expression to achieve a level similar to the MTM1 expression in the muscle of a healthy mammal.
A method of treating an X-linked myotubular myopathy (XLMTM) in a mammal with early onset of XLMTM pathology, the method comprising administering intramuscularly to the mammal a composition that increases the expression of myotubularin in a muscle of the mammal, wherein the composition comprises a viral vector comprising a nucleic acid sequence encoding an Myotubularin 1 (MTM1) gene operably linked to a muscle specific promoter.
Dependencies are inferred from the claim text.