Methods of treating fabry disease in patients having the G9331A mutation in the GLA gene
Provided are methods of treating a patient diagnosed with Fabry disease and methods of enhancing α-galactosidase A in a patient diagnosed with or suspected of having Fabry disease. Certain methods comprise administering to a patient a therapeutically effective dose of a pharmacological chaperone for α-galactosidase A, wherein the patient has a splice site mutation in intron 4 of the nucleic acid sequence encoding α-galactosidase A. Also described are uses of pharmacological chaperones for the treatment of Fabry disease and compositions for use in the treatment of Fabry disease.
1. A method of treating a patient diagnosed with Fabry disease, the method comprising administering to the patient a therapeutically effective dose of 1-deoxygalactonojirimycin or salt thereof, wherein the patient has a splice site mutation in the nucleic acid sequence encoding α-galactosidase A and the patient expresses at least some wild-type α-galactosidase A.
2. The method of claim 1 , wherein the mutation is relative to SEQ ID NO: 1.
3. The method of claim 1 , wherein the mutation is a splice site mutation in intron 4 of the nucleic acid sequence encoding α-galactosidase A.
4. The method of claim 1 , wherein the dose of 1-deoxygalactonojirimycin or salt thereof is from about 25 mg to about 250 mg.
5. The method of claim 1 , wherein the salt of 1-deoxygalactonojirimycin is 1-deoxygalactonojirimycin hydrochloride.
6. The method of claim 1 , wherein the dose is about 150 mg every other day of 1-deoxygalactonojirimycin hydrochloride or an equivalent dose of 1-deoxygalactonojirimycin or a salt thereof other than the hydrochloride salt.
7. The method of claim 1 , wherein the 1-deoxygalactonojirimycin or salt thereof is administered orally.
8. The method of claim 1 , wherein the 1-deoxygalactonojirimycin or salt thereof is administered by injection.
9. The method of claim 1 , where in the patient is male.
10. The method of claim 1 , where in the patient is female.
11. A method of treating a human patient diagnosed with Fabry disease, the method comprising administering to the patient a therapeutically effective dose of 1-deoxygalactonojirimycin or salt thereof, wherein the patient has a splice site mutation in the nucleic acid sequence encoding α-galactosidase A and the patient expresses at least some wild-type α-galactosidase A, and wherein the dose is about 25 to about 250 mg every other day of 1-deoxygalactonojirimycin hydrochloride, or an equivalent dose of 1-deoxygalactonojirimycin or a salt thereof other than the hydrochloride salt.
12. The method of claim 11 , wherein the mutation is relative to SEQ ID NO: 1.
13. The method of claim 11 , wherein the mutation is a splice site mutation in intron 4 of the nucleic acid sequence encoding α-galactosidase A.
14. The method of claim 11 , wherein the dose is about 150 mg every other day of 1-deoxygalactonojirimycin hydrochloride or an equivalent dose of 1-deoxygalactonojirimycin or a salt thereof other than the hydrochloride salt.
15. The method of claim 11 , wherein the salt of 1-deoxygalactonojirimycin is 1-deoxygalactonojirimycin hydrochloride.
16. The method of claim 11 , wherein the 1-deoxygalactonojirimycin or salt thereof is administered orally.
17. The method of claim 11 , wherein the 1-deoxygalactonojirimycin or salt thereof is administered by injection.
18. The method of claim 11 , where in the patient is male.
19. The method of claim 11 , where in the patient is female.