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AssigneeNationwide Children's Hospital, Inc.
InventorsBrian K. Kaspar, Jerry R. Mendell
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The present invention relates to methods for inhibiting myostatin, a regulator of muscle mass, for muscle enhancement (including inducing hypertrophy and/or hyperplasia) as well as improving muscle function (including decreasing atrophy and/or increasing endurance, force and/or strength). Some of the methods involve delivering genes to cells using gene delivery or other delivery techniques known in the art in order to inhibit myostatin. Examples of genes to be delivered are genes encoding proteins such as Follistatin, Follistatin-related gene-1 (FLRG-1), growth differentiation factor associated protein-1 (GASP-1) and myostatin precursor propeptide. The genes can be delivered using, for example, a recombinant Adeno-associated virus (rAAV), lentivirus or equine-associated virus capable of infecting the cells. Following introduction, the genes are expressed in the cell body of the infected cell and the encoded proteins are secreted systemically. In other methods of the invention, expression of proteins such as activin IIb and myostatin is inhibited by oligonucleotide techniques to effect muscle enhancement. All the methods have applications in the treatment of musculoskeletal and neurodegenerative disorders among others, as well as enhancing muscle in livestock.
A method of delivering a myostatin inhibitor to an animal in need thereof, comprising the step of administering to the animal a composition comprising one or more infectious encapsidated rAAVs, each comprising a recombinant AAV genome comprising at least one AAV inverted terminal repeat flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
A method of enhancing muscle in an animal in need thereof comprising the step of administering to the animal a composition comprising one or more infectious encapsidated rAAVs, each comprising a recombinant AAV genome comprising at least one AAV inverted terminal repeat flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
A method of improving muscle function in an animal in need thereof comprising the step of administering to the animal a composition comprising one or more infectious encapsidated rAAVs, each comprising a recombinant AAV genome comprising at least one AAV inverted terminal repeat flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
A method of treating a musculoskeletal disease in an animal in need thereof comprising administering to the animal one or more effective doses of a composition comprising one or more infectious encapsidated rAAVs, each comprising a recombinant AAV genome comprising at least one AAV inverted terminal repeat flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
A method of treating a neurodegenerative disease in which muscle is adversely affected in an animal in need thereof comprising administering to the animal one or more effective doses of a composition comprising one or more infectious encapsidated rAAVs, each comprising a recombinant AAV genome comprising at least one AAV inverted terminal repeat flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
A method of treating sarcopenia, cachexia, obesity, Type II diabetes, Pompe disease or lysosomal storage disorders in an animal in need thereof comprising administering to the animal one or more effective doses of a composition comprising one or more infectious encapsidated rAAVs, each comprising a recombinant AAV genome comprising AAV inverted terminal repeats flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
A recombinant adeno-associated virus (AAV) genome comprising at least one AAV inverted terminal repeat flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
An infectious encapsidated rAAV particle (rAAV) comprising a recombinant AAV genome comprising at least one AAV inverted terminal repeat flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
A packaging cell producing an infectious encapsidated rAAV comprising a recombinant AAV genome comprising at least one AAV inverted terminal repeat flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
A composition comprising one or more infectious encapsidated rAAVs, each comprising a recombinant AAV genome comprising at least one AAV inverted terminal repeat flanking a polynucleotide encoding a myostatin inhibitor, wherein the genome lacks AAV rep and cap DNA.
The rAAV follistatin-344 comprising the DNA sequence of SEQ ID NO:
The rAAV MCK follistatin-344 comprising the DNA sequence of SEQ ID NO:
Dependencies are inferred from the claim text.