Method to predict response to pharmacological chaperone treatment of diseases
The present invention provides methods to determine whether a patient with a lysosomal storage disorder will benefit from treatment with a specific pharmacological chaperone. The present invention exemplifies an in vitro method for determining α-galactosidase A responsiveness to a pharmacological chaperone such as 1-deoxygalactonojirimycin in a cell line expressing a mutant from of α-galactosidase A. The invention also provides a method for diagnosing Fabry disease in patients suspected of having Fabry disease.
1. A method of treating a patient diagnosed with Fabry disease which comprises administering to the patient a therapeutically effective dose of 1-deoxygalactonorjirimycin 1-deoxygalactonojirimycin, wherein the patient is identified as having a mutant mutation in α-galactosidase A, relative to a human α-galactosidase A encoded by a nucleic acid sequence set forth in SEQ ID NO:2, said mutation selected from the group consisting of the α-galactosidase A mutations A121T, A288D, A288P, A292P A348P, A73V, C52R, C94Y, D234E, D244H, D264Y, E338K, E341D, E398K, E48K, G271S, G35R, H225R, I219N, I242N, I270T, I303N, I317T, I354K, L14P, L243F, L300F, L310F, L45R, M267I, M76R, N224S, N298K, N298S, N320I, N34K, P205R, P259L, P265L, P265R, P293A, P293S, P409S, P40L, P40S, Q279R, Q280H, Q280K, Q321E, Q321R, Q327E, R301P, R49G, R49L, R49S, S201Y, S276N, S297C, S345P, V269M, W340R, W47L, and W95S.
2. The method of claim 1 wherein the patient is female.
3. The method of claim 1 , wherein 1-deoxygalactonojirimycin is in a pharmaceutically acceptable salt form.
4. The method of claim 3 , wherein the pharmaceutically acceptable salt form is 1-deoxygalactonojirimycin hydrochloride.
5. The method of claim 1, wherein the patient is male.
6. A method of treating a patient diagnosed with Fabry disease which comprises administering to the patient a therapeutically effective dose of 1-deoxygalactonojirimycin, wherein the patient is identified as having a mutation in α-galactosidase A, relative to a human α-galactosidase A encoded by a nucleic acid sequence set forth in SEQ ID NO:2, said mutation selected from the group consisting of the α-galactosidase A mutations A121T, A288P, A73V, D244H, D264Y, E338K, E398K, G271S, G35R, I219N, I242N, I270T, I303N, I317T, I354K, L243F, L300F, L310F, N224S, N298S, N320I, N34K, P259L, P265L, P409S, Q280H, Q280K, Q321R, Q327E, R301P, S201Y, S276N, S345P and V269M.
7. The method of claim 6, wherein the patient is female.
8. The method of claim 6, wherein 1-deoxygalactonojirimycin is in a pharmaceutically acceptable salt form.
9. The method of claim 8, wherein the pharmaceutically acceptable salt form is 1-deoxygalactonojirimycin hydrochloride.
10. The method of claim 6, wherein the patient is male.
11. The method of claim 6, wherein the mutation is A121T.
12. The method of claim 6, wherein the mutation is A288P.
13. The method of claim 6, wherein the mutation is A73V.
14. The method of claim 6, wherein the mutation is D244H.
15. The method of claim 6, wherein the mutation is D264Y.
16. The method of claim 6, wherein the mutation is E338K.
17. The method of claim 6, wherein the mutation is E398K.
18. The method of claim 6, wherein the mutation is G271S.
19. The method of claim 6, wherein the mutation is G35R.
20. The method of claim 6, wherein the mutation is I219N.
21. The method of claim 6, wherein the mutation is I242N.
22. The method of claim 6, wherein the mutation is I270T.
23. The method of claim 6, wherein the mutation is I303N.
24. The method of claim 6, wherein the mutation is I317T.
25. The method of claim 6, wherein the mutation is I354K.
26. The method of claim 6, wherein the mutation is L243F.
27. The method of claim 6, wherein the mutation is L300F.
28. The method of claim 6, wherein the mutation is L310F.
29. The method of claim 6, wherein the mutation is N224S.
30. The method of claim 6, wherein the mutation is N298S.
31. The method of claim 6, wherein the mutation is N320I.
32. The method of claim 6, wherein the mutation is N34K.
33. The method of claim 6, wherein the mutation is P259L.
34. The method of claim 6, wherein the mutation is P265L.
35. The method of claim 6, wherein the mutation is P409S.
36. The method of claim 6, wherein the mutation is Q280H.
37. The method of claim 6, wherein the mutation is Q280K.
38. The method of claim 6, wherein the mutation is Q321R.
39. The method of claim 6, wherein the mutation is Q327E.
40. The method of claim 6, wherein the mutation is R301P.
41. The method of claim 6, wherein the mutation is S201Y.
42. The method of claim 6, wherein the mutation is S276N.
43. The method of claim 6, wherein the mutation is S345P.
44. The method of claim 6, wherein the mutation is V269M.