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 or a salt thereof, wherein the patient is identified as having a mutant 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 D33Y, L36F, A37V, M42L, M42T, M42R, M51I, L54P, D55V, D55V/Q57L, C56F, C56Y, P60L, E66K, E66G, G85D, G85M, A97P, R118C, A135V, Y152C, A156T, W162G, F169S, G183A, Y184C, M187V, M187T, L191Q, V199M, P205S, P205L, N215D, Y216D, Y216C, S238N, I239T, L243W, S247C, Q250P, I253T, 254del1, A257P, V269A, P293T, R301G, A309P, D313G, Q321L, G325S, V339E, E358G, I359T, G360S, G360D, P362L, 401ins/T401S, P409T, T410A, T410I and G411D.
2. The method of claim 1 , wherein the mutation is selected from the group consisting of: D33Y, L36F, A37V, M42L and M42T.
3. The method of claim 1 , wherein the mutation is selected from the group consisting of: M42R, M51I, L54P, D55V and D55V/Q57L.
4. The method of claim 1 , wherein the mutation is selected from the group consisting of: C56F, C56Y, P60L, E66K and E66G.
5. The method of claim 1 , wherein the mutation is selected from the group consisting of: G85D, G85M, A97P, R118C and A135V.
6. The method of claim 1 , wherein the mutation is selected from the group consisting of: Y152C, A156T, W162G, F169S and G183A.
7. The method of claim 1 , wherein the mutation is selected from the group consisting of: Y184C, M187V, M187T, L191Q and V199M.
8. The method of claim 1 , wherein the mutation is selected from the group consisting of: P205S, P205L, N215D, Y216D and Y216C.
9. The method of claim 1 , wherein the mutation is selected from the group consisting of: S238N, I239T, L243W, S247C and Q250P.
10. The method of claim 1 , wherein the mutation is selected from the group consisting of: I253T, 254del1, A257P, V269A and P293T.
11. The method of claim 1 , wherein the mutation is selected from the group consisting of: R301G, A309P, D313G and Q321L.
12. The method of claim 1 , wherein the mutation is selected from the group consisting of: G325S, V339E, E358G and I359T.
13. The method of claim 1 , wherein the mutation is selected from the group consisting of: G360S, G360D, P362L and 401ins/T401S.
14. The method of claim 1 , wherein the mutation is selected from the group consisting of: P409T, T410A, T410I and G411D.
15. The method of claim 1 , wherein the patient is male.
16. The method of claim 1 , wherein the patient is female.
17. The method of claim 1 , wherein the 1-deoxygalactonojirimycin is in a pharmaceutically acceptable salt form.
18. The method of claim 17 , wherein the pharmaceutically acceptable salt form is 1-deoxygalactonojirimycin hydrochloride.