Method and composition for treating arginase 1 deficiency
A method and composition to treat a subject with arginase 1 (ARG1) deficiency (ARG1-D) and to rapidly reduce the levels of at least one of arginine and/or a guanidino compound in the subject.
1. A method of treating Arginase 1 (ARG1) deficiency (ARG1-D) in a human patient in need thereof, the method comprising weekly administering a human arginase I having a cobalt metal cofactor to the patient, wherein the human arginase I is administered either intravenously at a weekly dose of about 0.005 to about 0.15 mg/kg or intramuscularly or subcutaneously at a weekly dose of about 0.01 to about 0.15 mg/kg.
2. The method of claim 1 , wherein the human arginase I comprises an amino acid sequence substantially identical to SEQ ID NO: 2.
3. The method of claim 1 , wherein the human arginase I is pegylated.
4. The method of claim 2 , wherein the human arginase I is pegylated.
5. The method of claim 1 , wherein the human arginase I is administered intravenously at a weekly dose of about 0.01 to about 0.1 mg/kg.
6. The method of claim 2 , wherein the human arginase 1 is administered intravenously at a weekly dose of about 0.01 to about 0.1 mg/kg.
7. The method of claim 3 , wherein the human arginase I is administered intravenously at a weekly dose of about 0.01 to about 0.1 mg/kg.
8. The method of claim 4 , wherein the human arginase I is administered intravenously at a weekly dose of about 0.01 to about 0.1 mg/kg.
9. The method of claim 1 , wherein the human arginase I is administered intravenously at a weekly dose of about 0.015, about 0.03 or about 0.06 mg/kg.
10. The method of claim 2 , wherein the human arginase I is administered intravenously at a weekly dose of about 0.015, about 0.03 or about 0.06 mg/kg.
11. The method of claim 3 , wherein the human arginase I is administered intravenously at a weekly dose of about 0.015, about 0.03 or about 0.06 mg/kg.
12. The method of claim 4 , wherein the human arginase I is administered intravenously at a weekly dose of about 0.015, about 0.03 or about 0.06 mg/kg.
13. The method of claim 1 , wherein the human arginase I is administered subcutaneously at a weekly dose of about 0.01 to about 0.1 mg/kg.
14. The method of claim 2 , wherein the human arginase I is administered subcutaneously at a weekly dose of about 0.01 to about 0.1 mg/kg.
15. The method of claim 3 , wherein the human arginase I is administered subcutaneously at a weekly dose of about 0.01 to about 0.1 mg/kg.
16. The method of claim 4 , wherein the human arginase I is administered subcutaneously at a weekly dose of about 0.01 to about 0.1 mg/kg.
17. The method of claim 1 , wherein the human arginase I is administered subcutaneously at a weekly dose of about 0.015, about 0.03 or about 0.06 mg/kg.
18. The method of claim 2 , wherein the human arginase I is administered subcutaneously at a weekly dose of about 0.015, about 0.03 or about 0.06 mg/kg.
19. The method of claim 3 , wherein the human arginase I is administered subcutaneously at a weekly dose of about 0.015, about 0.03 or about 0.06 mg/kg.
20. The method of claim 4 , wherein the human arginase I is administered subcutaneously at a weekly dose of about 0.015, about 0.03 or about 0.06 mg/kg.
21. The method of claim 1 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
22. The method of claim 2 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
23. The method of claim 3 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
24. The method of claim 4 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
25. The method of claim 5 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
26. The method of claim 6 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
27. The method of claim 7 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
28. The method of claim 8 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
29. The method of claim 9 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
30. The method of claim 10 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
31. The method of claim 11 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
32. The method of claim 12 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
33. The method of claim 13 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
34. The method of claim 14 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
35. The method of claim 15 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
36. The method of claim 16 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
37. The method of claim 17 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
38. The method of claim 18 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
39. The method of claim 19 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
40. The method of claim 20 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
41. A method of treating Arginase 1 (ARG1) deficiency (ARG1-D) in a human patient in need thereof, the method comprising weekly administering a human arginase I having a cobalt metal cofactor to the patient, wherein the human arginase I comprises an amino acid sequence substantially identical to SEQ ID NO: 2, wherein the human arginase I is administered intravenously initially at a dose about 0.005 to about 0.15 mg/kg and weekly thereafter administered either subcutaneously or intravenously to the patient.
42. The method of claim 41 , wherein the human arginase I is pegylated.
43. The method of claim 41 , wherein the arginase is administered initially at a dose about 0.01 to about 0.1 mg/kg.
44. The method of claim 42 , wherein the arginase is administered initially at a dose about 0.01 to about 0.1 mg/kg.
45. The method of claim 41 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.
46. The method of claim 42 , wherein the human arginase I is formulated in a buffer comprising about 5 mM potassium phosphate, about 50 mM sodium chloride and about 1.5% glycerol (w/v) at a pH of about 7.4.