Methods for treating lysosomal acid lipase deficiency in patients
View Patent ↗The present invention provides methods of treating LAL deficiency comprising administering to a mammal a therapeutically effective amount of lysosomal acid lipase with an effective dosage frequency. Methods of improving growth and liver function, increasing LAL tissue concentration, and increasing LAL activity in a human patient suffering from LAL deficiency are also provided.
1. A method of treating a human patient suffering from a lysosomal acid lipase (LAL) deficiency, comprising administering a recombinant human LAL to said human patient in an amount effective to reduce the serum or blood level of a liver transaminase to a normal level, wherein the recombinant human LAL is administered between one time about every 7 days and one time about every 30 days and the administration is sufficient to reduce liver damage of said human patient.
2. The method of claim 1 , wherein said liver transaminase is selected from the group consisting of a serum aspartate transaminase (AST) and an alanine transaminase (ALT).
3. The method of claim 1 , wherein said liver transaminase is AST.
4. The method of claim 1 , wherein said liver transaminase is ALT.
5. The method of claim 1 , wherein said administration is sufficient to improve hepatomegaly.
6. The method of claim 1 , wherein said administration is sufficient to increase serum hemoglobin levels.
7. The method of claim 1 , wherein said administration is sufficient to decrease liver size.
8. The method of claim 1 , wherein said administration is sufficient to decrease serum ferritin levels.
9. The method of claim 1 , wherein said recombinant human LAL is administered one time about every 7 days.
10. The method of claim 1 , wherein said recombinant human LAL is administered one time about every 14 days.
11. The method of claim 1 , wherein said human patient suffers from Wolman disease.
12. The method of claim 1 , wherein said human patient suffers from cholesteryl ester storage disease.
13. The method of claim 1 , wherein said recombinant human LAL comprises at least one terminal mannose or at least one terminal mannose-6-phosphate.
14. The method of claim 1 , wherein said amount effective to reduce the serum or blood level of a liver transaminase to the normal level is about 1 mg per kilogram body weight of said human patient.
15. The method of claim 1 , wherein serum half-life (t 1/2 ) of said recombinant human LAL is less than about 20 minutes.
16. The method of claim 1 , wherein serum half-life (t 1/2 ) of said recombinant human LAL is about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 minutes.
17. The method of claim 1 , wherein C max of said recombinant human LAL is about 200 ng to about 800 ng per mL of serum.
18. The method of claim 1 , wherein C max of said recombinant human LAL is at least 200 ng per mL of serum.
19. The method of claim 1 , wherein said recombinant human LAL is administered intravenously.
20. The method of claim 19 , wherein said recombinant human LAL is administered by infusion.
21. The method of claim 20 , wherein said human patient is infused for about one to about four hours.
22. The method of claim 1 , wherein said administration is sufficient to reduce lymphadenopathy.
23. The method of claim 1 , wherein said human patient is less than 1 year of age and said administration is sufficient to increase growth velocity of said human patient.
24. The method of claim 1 , further comprising administering a second therapeutic.
25. The method of claim 24 , wherein said second therapeutic is a cholesterol-reducing drug.
26. The method of claim 25 , wherein said second therapeutic is a statin.
27. The method of claim 25 , wherein said second therapeutic is ezetimibe.
28. The method of claim 24 , wherein said second therapeutic is an immunosuppressant.
29. The method of claim 24 , wherein said second therapeutic is an antihistamine.
30. The method of claim 29 , wherein said antihistamine is diphenhydramine.
31. The method of claim 30 , wherein said diphenhydramine is administered in an amount of about 1 to about 5 mg per kilogram body weight of said human patient.
32. The method of claim 30 , wherein said diphenhydramine is administered about 20 to about 90 minutes prior to said administration of recombinant human LAL.