US2010322942A1PendingUtilityA1

Therapeutic and prophylactic methods for neuromuscular disorders

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Assignee: WYETH LLCPriority: Jun 2, 2003Filed: Aug 27, 2010Published: Dec 23, 2010
Est. expiryJun 2, 2023(expired)· nominal 20-yr term from priority
Inventors:Lisa-Anne WhittemoreXiangping Li
A61P 37/02A61P 9/04A61P 43/00A61P 37/06A61P 37/08A61P 29/00A61P 25/02A61P 25/00A61P 3/14A61P 21/04A61P 19/02A61K 2039/505A61P 17/06C07K 16/24A61K 39/39533A61P 17/00A61P 11/00A61P 21/00A61K 31/573C07K 16/18A61K 39/395
41
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Claims

Abstract

The disclosure provides methods for treating neuromuscular disorders in mammals. The disclosed methods include administering therapeutically effective amounts of a GDF-8 inhibitor and a corticosteroid to a subject susceptible to, or having, a neuromuscular disorder, so as to maintain desirable levels of muscle function.

Claims

exact text as granted — not AI-modified
1 . A method of treating a mammal with a decrease of muscle function, comprising administering to the mammal a therapeutically effective amount of at least one GDF-8 inhibitor and a therapeutically effective amount of at least one corticosteroid in the amounts and for a period of time sufficient to treat decrease of muscle function. 
     
     
         2 . The method of  claim 1 , wherein the muscle function of at least one muscle is evaluated by at least one parameter chosen from muscle mass, muscle contraction force, serum CK concentration, or muscle morphology. 
     
     
         3 . The method of  claim 1 , wherein the muscle whose function is treated is chosen from at least one of gastrocnemius, tibialis anterior, quadriceps, extensor digitorum longus, cardiac muscle, or diaphragm muscle. 
     
     
         4 . The method of  claim 1 , wherein treating said mammal results in increased body weight of said mammal. 
     
     
         5 . The method of  claim 1 , wherein treating said mammal results in increased grip strength. 
     
     
         6 . The method of  claim 1 , wherein the mammal is human. 
     
     
         7 . The method of  claim 1 , wherein the corticosteroid is chosen from at least one of:
 (a) at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetonide;   (b) a derivative of at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetonide; or   (c) a pharmaceutically acceptable salt of at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetoniden.   
     
     
         8 . The method of  claim 1 , wherein the corticosteroid is prednisone or prednisolone. 
     
     
         9 . The method of  claim 1 , wherein the corticosteroid is administered at a dose between 0.1 and 2.0 mg/kg/day. 
     
     
         10 . The method of  claim 1 , wherein the corticosteroid is administered orally. 
     
     
         11 . The method of  claim 1 , wherein the method results in treating of cardiomyopathy of said mammal. 
     
     
         12 . The method of  claim 1 , wherein the administration of GDF-8 inhibitor and corticosteroid is concurrent. 
     
     
         13 . The method of  claim 1 , wherein the administration of GDF-8 inhibitor and corticosteroid is consecutive. 
     
     
         14 . The method of  claim 1 , wherein the GDF-8 inhibitor is a small molecule inhibitor. 
     
     
         15 . The method of  claim 1 , wherein the GDF-8 inhibitor is chosen from an antibody to GDF-8, an antibody to a GDF-8 receptor, a soluble GDF-8 receptor, a GDF-8 propeptide, follistatin, or a follistatin-domain-containing protein. 
     
     
         16 . The method of  claim 15 , wherein the antibody to GDF-8 is chosen from JA-16, Myo29, Myo28, or Myo22. 
     
     
         17 . The method of  claim 15 , wherein the GDF-8 propeptide is mutated at an aspartate residue. 
     
     
         18 . The method of  claim 15 , wherein the GDF-8 propeptide is joined to the Fc portion of an immunoglobulin. 
     
     
         19 . The method of  claim 15 , wherein the GDF-8 receptor is ActRIIB. 
     
     
         20 . The method of  claim 15 , wherein the GDF-8 receptor is joined to the Fc portion of an immunoglobulin. 
     
     
         21 . The method of  claim 15 , wherein the GDF-8 inhibitor is follistatin. 
     
     
         22 . The method of  claim 15 , wherein the follistatin-domain-containing protein is GASP-1. 
     
     
         23 . A method of treating muscle weakness, comprising administering to a mammal a therapeutically effective amount of at least one GDF-8 inhibitor and a therapeutically effective amount of at least one corticosteroid in the amounts and for a period of time sufficient to treat loss of muscle strength. 
     
     
         24 . The method of  claim 23 , wherein the mammal is human. 
     
     
         25 . The method of  claim 23 , wherein the corticosteroid is chosen from at least one of:
 (a) at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetonide;   (b) a derivative of at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetonide; or   (c) a pharmaceutically acceptable salt of at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetoniden.   
     
     
         26 . The method of  claim 23 , wherein the corticosteroid is prednisone or prednisolone. 
     
     
         27 . The method of  claim 23 , wherein the corticosteroid is administered at a dose between 0.1 and 2.0 mg/kg/day. 
     
     
         28 . The method of  claim 23 , wherein the corticosteroid is administered orally. 
     
     
         29 . The method of  claim 23 , wherein the GDF-8 inhibitor is a small molecule inhibitor. 
     
     
         30 . The method of  claim 23 , wherein the GDF-8 inhibitor is chosen from an antibody to GDF-8, an antibody to a GDF-8 receptor, a soluble GDF-8 receptor, a GDF-8 propeptide, follistatin, or a follistatin-domain-containing protein. 
     
     
         31 . The method of  claim 30 , wherein the antibody to GDF-8 is chosen from JA-16, Myo29, Myo28, or Myo22. 
     
     
         32 . The method of  claim 30 , wherein the GDF-8 propeptide is mutated at an aspartate residue. 
     
     
         33 . The method of  claim 30 , wherein the GDF-8 propeptide is joined to the Fc portion of an immunoglobulin. 
     
     
         34 . The method of  claim 30 , wherein the GDF-8 receptor is ActRIIB. 
     
     
         35 . The method of  claim 30 , wherein the GDF-8 receptor is joined to the Fc portion of an immunoglobulin. 
     
     
         36 . The method of  claim 30 , wherein the GDF-8 inhibitor is follistatin. 
     
     
         37 . The method of  claim 30 , wherein the follistatin-domain-containing protein is GASP-1. 
     
     
         38 . A method of treating corticosteroid-induced muscle atrophy, comprising administering to a mammal a therapeutically effective amount of at least one GDF-8 inhibitor sufficient to treat the corticosteroid-induced muscle atrophy. 
     
     
         39 . The method of  claim 38 , wherein the mammal is human. 
     
     
         40 . The method of  claim 38 , wherein the corticosteroid is chosen from at least one of:
 (a) at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetonide;   (b) a derivative of at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetonide; or   (c) a pharmaceutically acceptable salt of at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetoniden.   
     
     
         41 . The method of  claim 38 , wherein the corticosteroid is prednisone or prednisolone. 
     
     
         42 . The method of  claim 38 , wherein the corticosteroid is administered at a dose between 0.1 and 2.0 mg/kg/day. 
     
     
         43 . The method of  claim 38 , wherein the corticosteroid is administered orally. 
     
     
         44 . The method of  claim 38 , wherein the GDF-8 inhibitor is a small molecule inhibitor. 
     
     
         45 . The method of  claim 38 , wherein the GDF-8 inhibitor is chosen from an antibody to GDF-8, an antibody to a GDF-8 receptor, a soluble GDF-8 receptor, a GDF-8 propeptide, follistatin, or a follistatin-domain-containing protein. 
     
     
         46 . The method of  claim 45 , wherein the antibody to GDF-8 is chosen from JA-16, Myo29, Myo28, or Myo22. 
     
     
         47 . The method of  claim 45 , wherein the GDF-8 propeptide is mutated at an aspartate residue. 
     
     
         48 . The method of  claim 45 , wherein the GDF-8 propeptide is joined to the Fc portion of an immunoglobulin. 
     
     
         49 . The method of  claim 45 , wherein the GDF-8 receptor is ActRIIB. 
     
     
         50 . The method of  claim 45 , wherein the GDF-8 receptor is joined to the Fc portion of an immunoglobulin. 
     
     
         51 . The method of  claim 45 , wherein the GDF-8 inhibitor is follistatin. 
     
     
         52 . The method of  claim 45 , wherein the follistatin-domain-containing protein is GASP-1. 
     
     
         53 . A method of treating a neuromuscular disorder, comprising administering to a mammal having or at risk of the neuromuscular disorder a therapeutically effective amount of at least one GDF-8 inhibitor and a therapeutically effective amount of at least one corticosteroid in the amounts and for a period of time sufficient to treat the neuromuscular disorder. 
     
     
         54 . The method of  claim 53 , wherein the neuromuscular disorder is a muscular dystrophy. 
     
     
         55 . The method of  claim 54 , wherein the muscular dystrophy is Duchenne muscular dystrophy. 
     
     
         56 . The method of  claim 54 , wherein the muscular dystrophy is Becker muscular dystrophy. 
     
     
         57 . The method of  claim 53 , wherein the mammal is human. 
     
     
         58 . The method of  claim 53 , wherein the corticosteroid is chosen from at least one of:
 (a) at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetonide;   (b) a derivative of at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetonide; or   (c) a pharmaceutically acceptable salt of at least one of beclomethasone dipropionate, budesonide, cortisol, dexamethasone, fluticason propionate, mometasone furoate, prednisone, or triamcinolone acetoniden.   
     
     
         59 . The method of  claim 53 , wherein the corticosteroid is prednisone or prednisolone. 
     
     
         60 . The method of  claim 53 , wherein the corticosteroid is administered at a dose between 0.1 and 2.0 mg/kg/day. 
     
     
         61 . The method of  claim 53 , wherein the corticosteroid is administered orally. 
     
     
         62 . The method of  claim 53 , wherein the GDF-8 inhibitor is a small molecule inhibitor. 
     
     
         63 . The method of  claim 53 , wherein the GDF-8 inhibitor is chosen from an antibody to GDF-8, an antibody to a GDF-8 receptor, a soluble GDF-8 receptor, a GDF-8 propeptide, follistatin, or a follistatin-domain-containing protein. 
     
     
         64 . The method of  claim 63 , wherein the antibody to GDF-8 is chosen from JA-16, Myo29, Myo28, or Myo22. 
     
     
         65 . The method of  claim 63 , wherein the GDF-8 propeptide is mutated at an aspartate residue. 
     
     
         66 . The method of  claim 63 , wherein the GDF-8 propeptide is joined to the Fc portion of an immunoglobulin. 
     
     
         67 . The method of  claim 63 , wherein the GDF-8 receptor is ActRIIB. 
     
     
         68 . The method of  claim 63 , wherein the GDF-8 receptor is joined to the Fc portion of an immunoglobulin. 
     
     
         69 . The method of  claim 63 , wherein the GDF-8 inhibitor is follistatin. 
     
     
         70 . The method of  claim 63 , wherein the follistatin-domain-containing protein is GASP-1. 
     
     
         71 . The method of  claim 63 , wherein the method results in treating of cardiomyopathy of said mammal. 
     
     
         72 . The method of  claim 63 , wherein the administration of GDF-8 inhibitor and corticosteroid is concurrent. 
     
     
         73 . The method of  claim 63 , wherein the administration of GDF-8 inhibitor and corticosteroid is consecutive.

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