Medical use of the radical scavenger and antioxidant alpha-1-microglobulin
Medical use of alpha-1-microglobulin (A1M) in the treatment or prophylaxis of diseases wherein oxidative stress is a responsible factor in the progress of the disease. Notably, the present invention relates to the medical use of alpha-1-microglobulin in the treatment or prophylaxis of diseases or conditions associated with the presences of free radicals and/or free haemoglobin in the subject.
1. A method of treating a subject suffering from a disease or condition involving oxidative stress and reducing oxidant levels in a subject in need thereof, the method comprising administering to the subject an amount of alpha-1-microglobulin (A1M) effective to reduce oxidant levels in the subject of from about 0.5 mg/kg to about 100 mg/kg, wherein the disease or condition involving oxidative stress is selected from the group consisting of sepsis, inflammation, arthritis, hemolytic transfusion reaction, and diabetes.
2. A method of treating a subject suffering from a disease or condition associated with the presence of free haemoglobin in a body fluid and reducing free haemoglobin levels in a subject in need thereof, the method comprising administering to the subject an amount of alpha-1-microglobulin (A1M) effective to reduce free haemoglobin levels in the subject of from about 0.5 mg/kg to about 100 mg/kg, wherein the disease or condition associated with the presence of free haemoglobin in a body fluid is selected from the group consisting of sepsis, inflammation, arthritis, hemolytic transfusion reaction, and diabetes.
3. The method according to claim 1 , wherein A1M repairs or prevents oxidative damage by a combination of one or more different mechanisms.
4. The method according to claim 3 , wherein said mechanisms comprise one or more of enzymatic reduction, non-enzymatic reduction and/or radical scavenging.
5. The method according to claim 1 , wherein the A1M has an amino acid sequence with at least 85% identity with the amino acid sequence of human alpha-1-microglobulin set forth in SEQ ID NO: 1, including the following amino acid residues conserved from SEQ ID NO:1: Y22; C34; K69; K92; K118; K130; Y132; L180; I181; P182; and R183.
6. The method according to claim 5 , wherein the A1M has an amino acid sequence with at least 90% identity with SEQ ID NO: 1.
7. The method according to claim 1 , wherein the A1M is human alpha-1-microglobulin (SEQ ID NO: 1).
8. The method according to claim 1 , wherein the A1M has an amino acid sequence with at least 85% identity with the amino acid sequence of human recombinant alpha-1-microglobulin set forth in SEQ ID NO: 2, including the following amino acid residues conserved from SEQ ID NO: 2: Y40; C52; K87; K110; K136; K148; Y150; L198; I199; P200; and R201.
9. The method according to claim 8 , wherein the A1M has an amino acid sequence with at least 90% identity with SEQ ID NO: 2.
10. The method according to claim 1 , wherein the A1M is human recombinant alpha-1- microglobulin (SEQ ID NO: 2).
11. The method according to claim 1 , wherein the A1M is administered parenterally.
12. The method according to claim 1 , wherein the A1M is administered locally.
13. The method according to claim 1 , wherein the A1M is administered locally to a body cavity or to the skin.
14. The method according to claim 1 , wherein the A1M is administered in the form of a composition comprising the A1M and a pharmaceutically acceptable excipient.
15. The method according to claim 14 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of solvents, pH adjusting agents, osmotically active agents, co-solvents, solubilizing agents, emulsifying agents, suspending agents, surface active agents, and wetting agents.
16. The method according to claim 2 , wherein A1M repairs or prevents oxidative damage by a combination of one or more different mechanisms.
17. The method according to claim 16 , wherein said mechanisms comprise one or more of enzymatic reduction, non-enzymatic reduction and/or radical scavenging.
18. The method according to claim 2 , wherein the A1M has an amino acid sequence with at least 85% identity with the amino acid sequence of human alpha-1-microglobulin set forth in SEQ ID NO: 1, including the following amino acid residues conserved from SEQ ID NO:1: Y22; C34; K69; K92; K118; K130; Y132; L180; I181; P182; and R183.
19. The method according to claim 18 , wherein the A1M has an amino acid sequence with at least 90% identity with SEQ ID NO: 1.
20. The method according to claim 2 , wherein the A1M is human alpha-1-microglobulin (SEQ ID NO: 1).
21. The method according to claim 2 , wherein the A1M has an amino acid sequence with at least 85% identity with the amino acid sequence of human recombinant alpha-1-microglobulin set forth in SEQ ID NO: 2, including the following amino acid residues conserved from SEQ ID NO: 2: Y40; C52; K87; K110; K136; K148; Y150; L198; I199; P200; and R201.
22. The method according to claim 21 , wherein the A1M has an amino acid sequence with at least 90% identity with SEQ ID NO: 2.
23. The method according to claim 2 , wherein the A1M is human recombinant alpha-1-microglobulin (SEQ ID NO: 2).
24. The method according to claim 2 , wherein the A1M is administered parenterally.
25. The method according to claim 2 , wherein the A1M is administered locally.
26. The method according to claim 2 , wherein the A1M is administered locally to a body cavity or to the skin.
27. The method according to claim 2 , wherein the A1M is administered in the form of a composition comprising the A1M and a pharmaceutically acceptable excipient.
28. The method according to claim 27 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of solvents, pH adjusting agents, osmotically active agents, co-solvents, solubilizing agents, emulsifying agents, suspending agents, surface active agents, and wetting agents.