Pharmaceutical compositions and uses directed to lysosomal storage disorders

1. A method of treating a lysosomal storage disorder (LSD) or one or more symptoms associated with the LSD in a subject in need thereof comprising:

administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years,

wherein the LSD is chosen from Niemann-Pick type C disease, Tay-Sachs disease, the AB variant of Tay-Sachs disease, Sandhoff disease, Niemann-Pick type A disease, Niemann-Pick type B disease, Fabry disease, neuronal ceroid lipofuscinoses, Krabbe disease, Farber disease, Gaucher disease, metachromatic leukodystrophy, multiple sulphatase deficiency, mucolipidosis II, mucolipidosis III, MPS III, MPS VII, GM1 gangliosidosis, and aspartylglucosaminuria.

2. A method of delaying progression of a lysosomal storage disorder (LSD) or more symptoms associated with the LSD over time as compared to typical disease progression in a subject in need thereof comprising:

administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years.

3. A method of reversing progression of a lysosomal storage disorder (LSD) or one or more symptoms associated with the LSD over time in a subject in need thereof comprising:

administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years.

4. A method of improving in a subject in need thereof a biochemical marker of a lysosomal storage disorder (LSD) over time comprising:

administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years.

5. A method of reducing the severity of a lysosomal storage disorder (LSD) or reducing the severity of or eliminating one or more existing symptoms associated with the LSD in a subject in need thereof comprising:

administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject, wherein the LSD is not Niemann-Pick Type C.

6. A method of providing neuroprotection in a subject having, suspected of having, or at risk of having a lysosomal storage disorder (LSD) or one or more symptoms associated with the LSD comprising:

administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years.

7. A method of delaying or reversing progression of a lysosomal storage disorder (LSD) or reducing the severity of the LSD in a subject in need thereof comprising:

administering a therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof to the subject, wherein the LSD is not Niemann-Pick Type C and the subject is asymptomatic.

8. The method according to claim 4 , wherein the biochemical marker is increased lysosomal volume.

9. The method according to claim 1 , wherein the method comprises initiating administration of a therapeutically effective amount of acetyl-leucine to the subject in need thereof when the subject is asymptomatic.

10. The method according to claim 4 , wherein the initial administration occurs after the subject has been found to have a genetic and/or biochemical marker of the LSD.

11. The method according to claim 1 , wherein the acetyl-leucine is acetyl-DL-leucine.

12. The method according to claim 1 , wherein the acetyl-leucine has an enantiomeric excess of the L-enantiomer or the D-enantiomer.

13. The method according to claim 1 , wherein the acetyl-leucine is in a single enantiomeric form of either the L-enantiomer or the D-enantiomer.

14. The method according to claim 13 , wherein the single enantiomeric form is the L-enantiomer.

15. The method according to claim 1 , wherein the method comprises administering the acetyl-leucine to the subject in need thereof at a therapeutically effective amount of from about 1 g to about 15 g per day.

16. The method according to claim 1 , wherein the LSD is chosen from Niemann-Pick type A disease, Niemann-Pick type B disease, and Niemann-Pick type C disease.

17. The method according to claim 15 , wherein the method comprises administering the acetyl-leucine to the subject in need thereof at a therapeutically effective amount chosen from about 1 g to about 10 g per day, about 1.5 g to about 7 g per day, about 4 g to about 6 g per day, or about 4 g to about 5 g per day.

18. The method according to claim 1 , wherein the LSD is chosen from Tay-Sachs disease, Sandhoff disease, Niemann-Pick type A disease, Niemann-Pick type C disease, mucolipidosis II, MPS III, and GM1 gangliosidosis.

19. The method according to claim 2 , wherein the method comprises initiating administration of a therapeutically effective amount of acetyl-leucine to the subject in need thereof when the subject is asymptomatic.

20. The method according to claim 2 , wherein the therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof ranges from about 1 g to about 15 g per day.

21. The method according to claim 2 , wherein the LSD is chosen from Tay-Sachs disease, Sandhoff disease, Niemann-Pick type A disease, Niemann-Pick type C disease, mucolipidosis II, MPS III, and GM1 gangliosidosis.

22. The method according to claim 3 , wherein the therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof ranges from about 1 g to about 15 g per day.

23. The method according to claim 3 , wherein the LSD is chosen from Tay-Sachs disease, Sandhoff disease, Niemann-Pick type A disease, Niemann-Pick type C disease, mucolipidosis II, MPS III, and GM1 gangliosidosis.

24. The method according to claim 4 , wherein the method comprises initiating administration of a therapeutically effective amount of acetyl-leucine to the subject in need thereof when the subject is asymptomatic.

25. The method according to claim 4 , wherein the therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof ranges from about 1 g to about 15 g per day.

26. The method according to claim 4 , wherein the LSD is chosen from Tay-Sachs disease, Sandhoff disease, Niemann-Pick type A disease, Niemann-Pick type C disease, mucolipidosis II, MPS III, and GM1 gangliosidosis.

27. The method according to claim 5 , wherein the therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof ranges from about 1 g to about 15 g per day.

28. The method according to claim 5 , wherein the LSD is chosen from Tay-Sachs disease, Sandhoff disease, Niemann-Pick type A disease, Niemann-Pick type C disease, mucolipidosis II, MPS III, and GM1 gangliosidosis.

29. The method according to claim 6 , wherein the method comprises initiating administration of a therapeutically effective amount of acetyl-leucine to the subject in need thereof when the subject is asymptomatic.

30. The method according to claim 6 , wherein the therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof ranges from about 1 g to about 15 g per day.

31. The method according to claim 6 , wherein the LSD is chosen from Tay-Sachs disease, Sandhoff disease, Niemann-Pick type A disease, Niemann-Pick type C disease, mucolipidosis II, MPS III, and GM1 gangliosidosis.

32. The method according to claim 7 , wherein the therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof ranges from about 1 g to about 15 g per day.

33. The method according to claim 7 , wherein the LSD is chosen from Tay-Sachs disease, Sandhoff disease, Niemann-Pick type A disease, mucolipidosis II, MPS III, and GM1 gangliosidosis.

34. The method according to claim 7 , wherein the therapeutically effective amount of acetyl-leucine or a pharmaceutically acceptable salt thereof is administered to the subject for a duration chosen from at least about 3 months, at least about 6 months, at least about 1 year, at least about 2 years, and at least about 5 years.