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 D33G, L36W, Q57L, M96I, R112G, C174R, M187I, I253S, G258R, G271S/D313Y, D313Y, D322E, G325R, and R356Q.
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 G258R, G271S/D313Y, D313Y and R356Q.
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.