TREATMENT OF ARGINASE 1 DEFICIENCY
A method of treating Arginase 1 (ARG1) deficiency (ARG1-D) in a subject, comprising administering a pegzilarginase to the subject, wherein the pegzilarginase is a pegylated human arginase 1 comprising a cobalt metal cofactor, and wherein the pegzilarginase is administered weekly at a dose of from about 0.05 mg/kg to about 0.2 mg/kg.
1 . A method of treating Arginase 1 (ARG1) deficiency (ARG1-D) in a subject, the method comprising:
administering human arginase 1 to the subject,
wherein the human arginase 1 comprises a cobalt metal cofactor, and
wherein the human arginase 1 is administered weekly at a dose of from about 0.05 mg/kg to about 0.2 mg/kg of subject weight, and
after one or more weekly doses of the human arginase 1, increasing a daily amount of total protein intake in the subject as compared to when said subject is on an ARG1-D protein restricted diet.
2 .- 34 . (canceled)
35 . The method of claim 1 , comprising increasing the daily amount of total protein intake with at least 5%, 10%, 15%, 20%, 25% or 45% as compared to when on the protein restricted diet.
36 . The method of claim 1 , wherein increasing the daily amount of total protein intake comprises increasing the daily amount of natural protein intake such that the natural protein intake is at least 45%, 50%, 55%, 60%, 65% or 70% of the total protein intake.
37 . The method of claim 1 , further comprising, in addition to increasing the daily amount of total protein intake, reducing a daily intake of essential amino acids in the subject as compared to when on the protein restricted diet.
38 . The method of claim 1 , wherein the subject is an adult and the amount of total protein intake is increased to more than 40 g/day.
39 . The method of claim 1 , wherein the human arginase 1 is a pegylated human arginase 1.
40 . The method of claim 1 , wherein the human arginase 1 is administered subcutaneously, intravenously, intrathecally, intramuscularly, intratumorally, and/or intraperitoneally to the subject.
41 . The method of claim 1 , wherein the subject is co-administered an ammonia scavenger.
42 . The method of claim 41 , wherein the ammonia scavenger is a sodium benzoate and/or a glycerol phenylbutyrate.
43 . The method of claim 1 , wherein after one or more weekly doses of the human arginase 1, the subject's total consumed calories, total consumed protein/day, and total consumed natural protein, is increased by at least 15%.
44 . A combination therapy for use in treating a subject with Arginase 1 (ARG1) deficiency (ARG1-D), comprising:
human arginase 1 in a weekly dose of from about 0.05 mg/kg to about 0.2 mg/kg of subject weight, said arginase 1 comprising a cobalt metal cofactor, and
a daily amount of total protein that is higher than a daily amount of total protein for a subject with ARG1-D on a protein restricted diet.
45 . The combination therapy of claim 44 , wherein the daily amount of total protein comprises an amount of natural protein that is at least 5%, 10%, 15%, 20%, 25% or 45% of the daily amount of total protein.
46 . The combination therapy of claim 44 , wherein the daily amount of total protein is at least 45%, 50%, 55%, 60%, 65% or 70% of the total protein intake.
47 . The combination therapy of claim 44 , wherein the subject is an adult and the daily amount of total protein is greater than 40 g/day.
48 . The combination therapy of claim 44 , wherein the human arginase 1 is a pegylated human arginase 1.
49 . The combination therapy of claim 44 , further comprising an ammonia scavenger.
50 . The combination therapy of claim 49 , wherein the ammonia scavenger is a sodium benzoate and/or a glycerol phenylbutyrate.
51 . The combination therapy of claim 44 , further comprising a salt and/or a glycerol.
52 . The combination therapy of claim 51 , wherein the salt is NaCl, K 2 HPO 4 , KH 2 PO 4 , or any combination thereof.