Methods for treating inflammatory disorders and traumatic brain injury using stabilized non-hematopoietic EPO short peptides
The described invention provides methods for treating an inflammatory brain disease, disorder or condition and for treating a traumatic brain injury having an inflammatory component in a subject in need thereof using isolated erythropoietin (EPO)-derived oligopeptides.
1. A method for treating an inflammatory brain disease or traumatic brain injury in a subject, the method comprising:
(a) providing a pharmaceutical composition comprising:
(i) a therapeutically effective amount of at least one isolated erythropoietin (EPO)-derived oligopeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1 (JM-4), SEQ ID NO: 5, SEQ ID NO: 9 (JM-5), SEQ ID NO: 18, SEQ ID NO: 27, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO: 37; and
(ii) a pharmaceutically acceptable carrier;
(b) administering the pharmaceutical composition of (a) to the subject in need thereof, wherein the composition is effective in treating or alleviating the inflammatory brain disease or traumatic brain injury.
2. The method according to claim 1 , wherein the isolated erythropoietin (EPO)-derived oligopeptide is a cyclic peptide.
3. The method according to claim 1 , wherein the at least one isolated erythropoietin (EPO)-derived oligopeptide is a stabilized isolated erythropoietin (EPO)-derived oligopeptide, wherein the stabilized isolated erythropoietin (EPO)-derived oligopeptide comprises at least one small bicyclic compound added to either an N-terminal end or a C-terminal end of the isolated erythropoietin (EPO)-derived oligopeptide.
4. The method according to claim 1 , wherein the inflammatory brain disease is multiple sclerosis.
5. The method according to claim 1 , wherein the inflammatory brain disease is a demyelinating disease.
6. The method according to claim 1 , wherein the inflammatory brain disease is a chronic inflammatory brain disease.
7. The method according to claim 1 , wherein the inflammatory brain disease, disorder or condition is a complication following a traumatic brain injury (TBI).
8. The method according to claim 7 , wherein administering step (b) occurs within about 15 minutes after the traumatic brain injury.
9. The method according to claim 7 , wherein administering step (b) occurs within about 1 hour after the traumatic brain injury.
10. The method according to claim 7 , wherein administering step (b) occurs within about 3 hours after the traumatic brain injury.
11. The method according to claim 7 , wherein administering step (b) occurs within about 6 hours after the traumatic brain injury.
12. The method according to claim 7 , wherein administering step (b) occurs within 9 hours after the traumatic brain injury.
13. The method according to claim 7 , wherein administering step (b) occurs within about 24 hours of the traumatic brain injury.
14. The method according to claim 1 , wherein the method further comprises reducing infiltration of a population of a mononuclear cell into the brain of the subject.
15. The method according to claim 1 , further comprising maintaining a hematocrit at a stable level.
16. The method according to claim 1 , further comprising maintaining a hematocrit within about 20% of a reference value or baseline level.
17. A method for treating an inflammatory brain disease or traumatic brain injury in a subject, the method comprising:
(a) providing a pharmaceutical composition comprising:
(i) a therapeutically effective amount of at least one isolated erythropoietin (EPO)-derived oligopeptide of JM-4 (SEQ ID NO: 1) and JM-5 (SEQ ID NO: 9); and
(ii) a pharmaceutically acceptable carrier;
(b) administering the pharmaceutical composition of (a) to the subject in need thereof, wherein the composition is effective in treating or alleviating the inflammatory brain disease or traumatic brain injury.