Compositions and methods for the treatment of Zellweger spectrum disorder
Provided herein are methods of treating Zellweger spectrum disorder (ZSD) in a subject in need thereof or improving peroxisome assembly in a cell in need thereof comprising administering to the subject a therapeutically effective amount of Compounds of Formula I or II.
1. A method of treating Zellweger spectrum disorder comprising Zellweger Syndrome (ZS), neonatal adrenoleukodystrophy, or Refsum disease (IRD), in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound selected from naltriben, naltrindole, or a tautomer of each thereof, or a pharmaceutically acceptable salt of each of the foregoing.
2. The method of claim 1 , wherein the Zellweger spectrum disorder is caused by a PEX gene mutation.
3. The method of claim 2 , wherein the PEX gene mutation causes abnormal peroxisome assembly.
4. The method of claim 1 , wherein the compound is naltriben or naltrindole.
5. The method of claim 1 , wherein the compound is naltriben methanesulfonate hydrate.
6. The method of claim 1 , wherein the compound is naltrindole hydrochloride.
7. A method of improving peroxisome assembly in a cell in need thereof comprising administering to the cell a therapeutically effective amount of a compound selected from naltriben, naltrindole,
or a tautomer of each thereof, or a pharmaceutically acceptable salt of each of the foregoing.
8. The method of claim 7 , wherein the peroxisome assembly is improved by from about 20% to about 96%.
9. The method of claim 7 , wherein the peroxisome assembly is improved by at least 20%.
10. The method of claim 7 , wherein the peroxisome assembly is improved by at least 40%.
11. The method of claim 7 , wherein the peroxisome assembly is improved by at least 50%.
12. The method of claim 7 , wherein the compound is naltriben or naltrindole.
13. The method of claim 7 , wherein the compound is naltriben methanesulfonate hydrate.
14. The method of claim 7 , wherein the compound is naltrindole hydrochloride.
15. The method of claim 1 , further comprising detecting for the presence of the PEX gene mutation in a sample isolated from the subject prior to administration of the compound or a tautomer thereof, or a pharmaceutically acceptable salt of each of the foregoing.
16. The method of claim 1 , wherein the Zellweger spectrum disorder is caused by a misfolded PEX1 protein.