Methods Of Treating Fabry Disease In Patients Having A 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 mutation in 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 - 250 . (canceled)
251 . A molecule comprising migalastat bound to an α-galactosidase A protein comprising a HEK assay amenable mutation selected from the group consisting of N5D, N5K, P6L, P6Q, P6R, P6S, P6T, E7D, E7K, E7V, L8I, L8P, L8Q, H9L, H9Q, H9R, H9Y, L10M, L10P, L10Q, L10R, L10V, G11C, G11D, G11R, G11S, G11V, C12G, C12R, C12S, C12Y, A13E, A13G, L14F, L14H, L14V, R17C, R17G, R17H, R17P, R17S, F18I, F18L, A20G, L21H, V22A, V22F, V22I, V22L, S23P, S23T, W24S and D25H, wherein the residues are numbered relative to SEQ ID NO:2.
252 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: N5D and N5K.
253 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: P6L, P6Q, P6R, P6S and P6T.
254 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: E7D, E7K and E7V.
255 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: L8I, L8P and L8Q.
256 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: H9L, H9Q, H9R and H9Y.
257 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: L10M, L10P, L10Q, L10R and L10V.
258 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: G11C, G11D, G11R, G11S and G11V.
259 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: C12G, C12R, C12S and C12Y.
260 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: A13E and A13G.
261 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: L14F, L14H and L14V.
262 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: R17C, R17G, R17H, R17P and R17S.
263 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: F18I and F18L.
264 . The molecule of claim 251 , wherein the mutation is A20G.
265 . The molecule of claim 251 , wherein the mutation is L21H.
266 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: V22A, V22F, V221 and V22L.
267 . The molecule of claim 251 , wherein the mutation is selected from the group consisting of: S23P and S23T.
268 . The molecule of claim 251 , wherein the mutation is W24S.
269 . The molecule of claim 251 , wherein the mutation is D25H.
270 . The molecule of claim 251 , wherein the α-galactosidase A protein bound to migalastat has increased stability as compared to a naturally-occurring α-galactosidase A protein having the same mutation.