Methods of treating Fabry patients having renal impairment
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
1. A composition comprising migalastat bound to an α-galactosidase A protein comprising a HEK assay amenable mutation selected from the group consisting of A13T, A13P, N34D, N34T, G35V, M42K, E48Q, N53L, L54F, P60T, P60S, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, D165G, L167V, L180W, K185E, R196G, V199G, Y200C, E203V, E203D, Y207H, M208R, I219L, Q221P, N224T, I242T, Q250R, Q250H, A257G, G261S, G261C, G271D, W277G, W277C, M284V, I303F, A307T, D322N, K326N, G334E, F337S, W349S, A352V, E358Q, E358D, G361E, G375E, G395E, T412N, and M421V.
2. The composition of claim 1 , wherein the migalastat stabilizes the α-galactosidase A protein.
3. The composition of claim 1 , wherein the mutation is selected from the group consisting of A13P, L89F, Y200C, G271D, W277C and F337S.
4. The composition of claim 1 , wherein the composition further comprises globotriaosylceramide (GL-3).
5. The composition of claim 1 , wherein the composition comprises white blood cells containing the migalastat bound to the α-galactosidase A protein.
6. The composition of claim 1 , wherein the composition comprises plasma containing the migalastat bound to the α-galactosidase A protein.
7. The composition of claim 5 , wherein the plasma contains migalastat at a concentration in the range of about 1 ng/mL to about 2191 ng/mL.
8. The composition of claim 5 , wherein the plasma further comprises globotriaosylsphingosine (lyso-Gb 3 ).
9. The composition of claim 7 , wherein the plasma contains lyso-Gb 3 at a concentration in the range of about 9.3 to about 13.1 nM/L.
10. The composition of claim 1 , wherein the composition comprises an organ containing migalastat bound to the α-galactosidase A protein.
11. The composition of claim 10 , wherein the organ comprises a heart.
12. The composition of claim 10 , wherein the organ comprises a kidney.
13. The composition of claim 10 , wherein the organ comprises skin.
14. The composition of claim 1 , wherein the composition comprises tissue containing migalastat bound to the α-galactosidase A protein.
15. The composition of claim 1 , wherein the composition comprises cells containing migalastat bound to the α-galactosidase A protein.
16. The composition of claim 15 , wherein the migalastat is bound to the α-galactosidase A protein in the endoplasmic reticulum.
17. The composition of claim 16 , wherein the migalastat stabilizes the α-galactosidase A protein in the endoplasmic reticulum and facilitates the proper trafficking of the α-galactosidase A protein to lysosomes.
18. The composition of claim 1 , wherein the composition further comprises 4-MU-α-Gal.
19. The composition of claim 1 , wherein the composition contains migalastat at a concentration in the range of 17 nM to 1 mM.
20. The composition of claim 1 , wherein the composition contains migalastat at a concentration in the range of 10 μM.
21. The composition of claim 1 , wherein the mutation is a disease-causing mutation.