Treatment of muscular dystrophy
The present invention resides in the discovery that glucocorticoid receptor antagonists are effective for treating muscular dystrophy including type 1 or type 2 myotonic dystrophy. Treatment methods and kits are provided.
1. A method for treating a patient suffering from a muscular dystrophy selected from Duchenne Muscular Dystrophy, myotonic dystrophy 1 and myotonic dystrophy 2, comprising:
measuring the cortisol level of said patient; then
administering to the patient a first daily dose of between about 50 milligrams (mg) and about 500 mg of a glucocorticoid receptor antagonist, which inhibits cortisol binding to the glucocorticoid receptor, and binds to the glucocorticoid receptor with an affinity that is at least 100-fold higher than its binding affinity to the mineralocorticoid receptor, wherein said first daily dose is administered on a first day;
subsequently administering further daily doses of said glucocorticoid receptor antagonist to the patient for at least about 12 weeks to ameliorate the symptoms of the muscular dystrophy; and
measuring the cortisol level of the patient about two weeks after said first day, wherein the patient is not otherwise in need of treatment with a glucocorticoid receptor antagonist, and wherein said glucocorticoid receptor antagonist.
2. The method of claim 1 , wherein the patient suffers from Duchenne Muscular Dystrophy.
3. The method of claim 1 , wherein the patient suffers from myotonic dystrophy 1.
4. The method of claim 1 , wherein the patient suffers from myotonic dystrophy 2.
5. The method of claim 1 , wherein the glucocorticoid receptor antagonist comprises a steroidal skeleton with at least one phenyl-containing moiety in the 11-β position of the steroidal skeleton.
6. The method of claim 5 , wherein the phenyl-containing moiety in the 11-β position of the steroidal skeleton is a dimethylaminophenyl moiety.
7. The method of claim 6 , wherein the glucocorticoid receptor antagonist is mifepristone.
8. The method of claim 6 , wherein the glucocorticoid receptor antagonist is selected from the group consisting of 11β-(4-dimethylaminoethoxyphenyl)-17α-propynyl-17β-hydroxy-4,9 estradien-3-one and 17β-hydroxyl 7α-19-(4-methylphenyl)androsta-4,9(11)-dien-3-one.
9. The method of claim 1 , wherein the glucocorticoid receptor antagonist is selected from the group consisting 4α(S)-Benzyl-2(R)-prop-1-ynyl-1,2,3,4,4α,9,10,10α(R)-octahydro-phenanthrene-2,7-diol and 4α(S)-Benzyl-2(R)-chloroethynyl-1,2,3,4,4α,9,10,10α(R)-octahydro-phenanthrene-2,7-diol.
10. The method of claim 1 , wherein the glucocorticoid receptor antagonist is (11β,17β)-11-(1,3-benzodioxol-5-yl)-17-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one.
11. The method of claim 1 , wherein the glucocorticoid receptor antagonist is orally administered.
12. The method of claim 1 , wherein the glucocorticoid receptor antagonist is administered by transdermal application, by a nebulized suspension, or by an aerosol spray.