Compositions and methods for the treatment of lysosomal storage disorders and disorders characterized by lysosomal dysfunction
The present invention relates to compositions and methods of treating lysosomal storage diseases and methods of using trehalose.
1. A method of treating juvenile Neuronal Ceroid Lipofuscinosis in a subject in need thereof, the method comprising administering a therapeutically effective amount of a composition comprising a protein kinase B inhibitor.
2. The method of claim 1 , wherein the protein kinase B inhibitor is selected from trehalose and MK-2206.
3. The method of claim 1 , wherein the protein kinase B inhibitor is trehalose.
4. The method of claim 3 , wherein the composition comprises a single active ingredient for inhibiting protein kinase B consisting of trehalose.
5. The method of claim 3 , wherein the composition further comprises a trehalase inhibitor.
6. The method of claim 5 , wherein the trehalase inhibitor is miglustat.
7. The method of claim 6 , wherein the miglustat is administered at a dosage range from about 30 to about 100 mg/Kg, about 100 to about 300 mg/Kg, or about 100 to about 150 mg/Kg.
8. The method of claim 1 , wherein the trehalose is a trehalose analog.
9. The method of claim 8 , wherein the trehalose analog is selected from lentztrehalose A, lentztrehalose B, and lentztrehalose C.
10. The method of claim 3 , wherein the composition is administered parenterally at a per administration dose of between 0.1 g/kg to 1 g/kg trehalose.
11. The method of claim 10 , wherein the administration is completed within less than 120 minutes.
12. The method of claim 6 , wherein the composition is administered parenterally at a per administration dose of between 0.1 g/kg to 1 g/kg trehalose and a per administration dose of the miglustat ranging from about 30 to about 100 mg/Kg, about 100 to about 300 mg/Kg, or about 100 to about 150 mg/Kg.
13. The method of claim 3 , wherein the composition is administered orally at a per administration dose of between 0.1 g/kg to 1 g/kg trehalose.
14. The method of claim 6 , wherein the composition is administered orally at a per administration dose of between 0.1 g/kg to 1 g/kg trehalose and a per administration dose of the miglustat ranging from about 30 to about 100 mg/Kg, about 100 to about 300 mg/Kg, or about 100 to about 150 mg/Kg.
15. The method of claim 3 , wherein the composition is administered once daily.
16. The method of claim 3 , wherein the composition is administered twice daily.
17. The method of claim 1 , wherein the protein kinase B inhibitor is MK-2206.
18. The method of claim 17 , wherein the composition comprises about 30 to about 100 mg MK-2206.
19. The method of claim 17 , wherein the composition comprises about 100 to about 300 mg MK-2206.
20. The method of claim 17 , wherein the composition is administered parenterally.
21. The method of claim 20 , wherein the composition is administered at a per administration dose of about 100 mg/kg to about 150 mg/kg MK-2206.
22. The method of claim 20 , wherein the composition is administered once daily.
23. The method of claim 20 , wherein the composition is administered twice daily.
24. A method of using trehalose, the method comprising inhibiting the activity of a protein kinase B by contacting the protein kinase B with a composition comprising trehalose, wherein the method is used to treat juvenile Neuronal Ceroid Lipofuscinosis.
25. A method of enhancing clearance of undegraded material in a cell exhibiting dysfunctional lysosomal clearance, the method comprising inhibiting a protein kinase B in the cell by contacting the cell with a composition comprising a protein kinase B inhibitor, wherein the protein kinase B inhibitor is MK-2206.
26. A method of treating a lysosomal storage disorder or disorder characterized by lysosomal dysfunction in a subject in need thereof, the method comprising administering a therapeutically effective amount of a composition comprising MK-2206.