ACTH prophylactic treatment of renal disorders
View Patent ↗Provided herein are methods for prophylactic treatment of renal disorders comprising administration of adrenocorticotropic hormone (ACTH), or fragment, analog, complex or aggregate thereof, or any combination thereof, to an individual suspected of having, predisposed to, or at risk of developing a renal disorder.
1. A method of prophylactically treating acute kidney injury (AKI) in an individual in need thereof comprising selecting an individual suspected of having, predisposed to, or at risk of developing acute kidney injury and administering an adrenocorticotropic hormone (ACTH) peptide to the individual in need thereof, wherein the ACTH peptide is administered as a first dose and one or more subsequent doses; and
wherein the ACTH peptide is selected from the group consisting of:
(a) the ACTH 1-39 peptide consisting of the sequence:
(SEQ ID NO: 1)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-
11 12 13 14 15 16 17 18 19 20
Lys-Val-Tyr-Pro-Asp-Gly-Ala-Glu-Asp-Gln-
21 22 23 24 25 26 27 28 29 30
Leu-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe-OH;
31 32 33 34 35 36 37 38 39
(b) the ACTH 1-24 peptide consisting of the sequence:
(SEQ ID NO: 2)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-
11 12 13 14 15 16 17 18 19 20
Lys-Val-Tyr-Pro; and
21 22 23 24
(c) the ACTH peptide is ACTH 1-17 peptide consisting of the sequence of:
(SEQ ID NO: 3)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg.
11 12 13 14 15 16 17
2. The method of claim 1 , wherein the ACTH peptide is ACTH 1-39 peptide consisting of the sequence:
(SEQ ID NO: 1)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-
11 12 13 14 15 16 17 18 19 20
Lys-Val-Tyr-Pro-Asp-Gly-Ala-Glu-Asp-Gln-
21 22 23 24 25 26 27 28 29 30
Leu-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe-OH.
31 32 33 34 35 36 37 38 39
3. The method of claim 1 , wherein the ACTH peptide is ACTH 1-24 peptide consisting of the sequence:
(SEQ ID NO: 2)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-
11 12 13 14 15 16 17 18 19 20
Lys-Val-Tyr-Pro.
21 22 23 24
4. The method of claim 1 , wherein the ACTH peptide is ACTH 1-17 peptide consisting of the sequence:
(SEQ ID NO: 3)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg.
11 12 13 14 15 16 17
5. The method of claim 1 , wherein the individual is undergoing surgery.
6. The method of claim 1 , wherein the individual has sepsis.
7. The method of claim 1 , wherein the first dose of ACTH peptide comprises a dose between about 10 IU and about 150 IU, and the one or more subsequent doses of ACTH peptide is administered about every day, about every 2 days, about every 5 days, about every week, about every two weeks, about every three weeks, about every month, about every two months, or any combination thereof.
8. The method of claim 1 , wherein the first dose of ACTH peptide comprises a dose between about 10 IU and about 150 IU, and the one or more subsequent doses of ACTH peptide are between about 20%-80% of the first dose.
9. The method of claim 1 , wherein the first dose of ACTH peptide comprises a first dose of between about 10 IU and about 150 IU, and the one or more subsequent doses of ACTH peptide are between about 20%-60% of the first dose.
10. The method of claim 1 , wherein the first dose of ACTH peptide comprises a first dose of between about 10 IU and about 150 IU, and the one or more subsequent doses of ACTH peptide are between about 10 IU and about 80 IU.
11. The method of claim 1 , wherein the ACTH peptide is a porcine ACTH peptide, a human ACTH peptide, or a recombinant ACTH peptide.
12. A method of treating renal damage caused by ischemia to the kidney in an individual in need thereof comprising administering an adrenocorticotropic hormone (ACTH) peptide to the individual in need thereof, wherein the ACTH peptide is administered as a first dose and one or more subsequent doses; and
wherein the ACTH peptide is selected from the group consisting of:
(a) the ACTH 1-39 peptide consisting of the sequence:
(SEQ ID NO: 1)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-
11 12 13 14 15 16 17 18 19 20
Lys-Val-Tyr-Pro-Asp-Gly-Ala-Glu-Asp-Gln-
21 22 23 24 25 26 27 28 29 30
Leu-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe-OH;
31 32 33 34 35 36 37 38 39
(b) the ACTH 1-24 peptide consisting of the sequence:
(SEQ ID NO: 2)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-
11 12 13 14 15 16 17 18 19 20
Lys-Val-Tyr-Pro; and
21 22 23 24
(c) the ACTH peptide is ACTH 1-17 peptide consisting of the sequence:
(SEQ ID NO: 3)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg.
11 12 13 14 15 16 17
13. The method of claim 12 , wherein the ACTH peptide is ACTH 1-39 peptide consisting of the sequence:
(SEQ ID NO: 1)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-
11 12 13 14 15 16 17 18 19 20
Lys-Val-Tyr-Pro-Asp-Gly-Ala-Glu-Asp-Gln-
21 22 23 24 25 26 27 28 29 30
Leu-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe-OH.
31 32 33 34 35 36 37 38 39
14. The method of claim 12 , wherein the ACTH peptide is ACTH 1-24 peptide consisting of the sequence:
(SEQ ID NO: 2)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-
11 12 13 14 15 16 17 18 19 20
Lys-Val-Tyr-Pro.
21 22 23 24
15. The method of claim 12 , wherein the ACTH peptide is ACTH 1-17 peptide consisting of the sequence:
(SEQ ID NO: 3)
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg.
11 12 13 14 15 16 17
16. The method of claim 12 , wherein the selection of an individual is based upon a decrease in glomerular filtration rate (GFR) as compared to a normal baseline level, an increase in serum creatinine as compared to a normal baseline level, an increase in urinary protein as compared to a normal baseline level, an elevated asymmetric dimethylarginine (ADMA) as compared to a normal baseline level, an elevated cystatin C (CysC) as compared to a normal baseline level, an elevated C-reactive Protein (CRP) as compared to a normal baseline level, or an elevated soluble tumor necrosis factor receptor II (sTNFrii) as compared to a normal baseline level.