Method of treatment of hypoxia inducible factor (HIF)-related conditions
The present invention relates to methods of treatment of Hypoxia Inducible Factor (HIF)-related conditions, and in particular to methods of treatment of HIF-related conditions comprising the administration of a composition comprising transferrins.
1. A method of treating a Hypoxia Inducible Factor (HIF)-related pathological condition in a patient in need thereof, wherein the HIF-related pathological condition is Middle Cerebral Artery occlusion (MCAo), comprising administering to the patient a composition comprising a therapeutically effective amount of transferrin, and wherein the transferrin is a mixture of apo-transferrin and holo-transferrin in a ratio from 99% Apo-Tf:1% Holo-Tf to 30% Apo-Tf:70% Holo-Tf.
2. The method of claim 1 , wherein the composition further comprises an iron chelator or prolyl hydroxylase domain-containing protein 2 (PHD2) enzyme inhibitor.
3. The method of claim 2 , wherein the iron chelator is selected from the group consisting of M30, deferoxamine (DFO), Deferasirox, deferiprone, deferitrin, L1NAll, CP363, CP502 and Ethylenediaminetetraacetic acid (EDTA).
4. The method of claim 2 , wherein the PHD2 enzyme inhibitor is selected from the group consisting of IOX2, IOX3 and dimethyloxallylglycine.
5. The method of claim 1 , wherein the patient is a transplant recipient of an organ.
6. The method of claim 5 , wherein the organ has been treated with the composition in preparation for the transplantation into the recipient.
7. The method of claim 6 , where the composition further comprises an iron chelator or prolyl hydroxylase domain-containing protein 2 (PHD2) enzyme inhibitor.
8. The method of claim 1 , wherein the condition is associated with ischemia or oxygen deprivation in the patient prior to surgery.
9. The method of claim 8 , wherein the ischemia is due to cardiac arrest, thrombotic clots, traumatic injury or stroke.
10. The method of claim 1 , wherein the condition is associated with interruption of blood flow during a surgical intervention in the patient.
11. The method of claim 1 , wherein the transferrin is recombinant.
12. The method of claim 1 , wherein the transferrin is modified by pegylation, glycosylation or polysialylation to extend its plasma half-life.
13. The method of claim 1 , wherein the composition further comprises an iron chelator.
14. The method of claim 1 , wherein the neurodegenerative disease is Parkinson's disease.
15. The method of claim 1 , wherein the neurodegenerative disease is Alzheimer's disease.
16. The method of claim 1 , wherein the neurodegenerative disease is Amvlotrophic Lateral Sclerosis.
17. The method of claim 1 , wherein the transferrin is recombinant.
18. The method of claim 1 , wherein the transferrin is modified by pegylation, glvcosvlation or polvsialvlation to extend its plasma half-life.
19. The method of claim 1 , wherein the transferrin comprises an amino acid sequence with at least 80% identity to SEQ ID NO: 1.
20. The method of claim 1 , wherein the transferrin comprises an amino acid sequence with at least 90% identity to SEQ ID NO: 1.
21. A method of treating a Hypoxia Inducible Factor (HIF)-related pathological condition in a patient in need thereof, wherein the HIF-related pathological condition is a neurodegenerative disease selected from the group consisting of Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amylotrophic Lateral Sclerosis, comprising administering to the patient a composition comprising a therapeutically effective amount of transferrin, wherein the transferrin comprises an amino acid sequence with at least 70% identity to SEQ ID NO: 1 and wherein the transferrin is a mixture of apo-transferrin and holo-transferrin in a ratio from 99% Apo-Tf:1% Holo-Tf to 30% Apo-Tf:70% Holo-Tf.
22. The method of claim 21 , wherein the composition further comprises an iron chelator or prolyl hydroxylase domain-containing protein 2 (PHD2) enzyme inhibitor.
23. The method of claim 22 , wherein the iron chelator is selected from the group consisting of M30, deferoxamine (DFO), Deferasirox, deferiprone, deferitrin, L1NAll, CP363, CP502 and Ethylenediaminetetraacetic acid (EDTA).
24. The method of claim 22 , wherein the PHD2 enzyme inhibitor is selected from the group consisting of IOX2, IOX3 and dimethyloxallylglycine.
25. The method of claim 21 , wherein the patient is a transplant recipient of an organ.
26. The method of claim 25 , wherein the organ has been treated with the composition in preparation for the transplantation into the recipient.
27. The method of claim 26 , where the composition further comprises an iron chelator or prolyl hydroxylase domain-containing protein 2 (PHD2) enzyme inhibitor.
28. The method of claim 21 , wherein the condition is associated with ischemia or oxygen deprivation in the patient prior to surgery.
29. The method of claim 28 , wherein the ischemia is due to cardiac arrest, thrombotic clots, traumatic injury or stroke.
30. The method of claim 21 , wherein the condition is associated with interruption of blood flow during a surgical intervention in the patient.
31. The method of claim 21 , wherein the transferrin is recombinant.
32. The method of claim 21 , wherein the transferrin is modified by pegylation, glycosylation or polysialylation to extend its plasma half-life.
33. The method of claim 21 , wherein the composition further comprises an iron chelator.
34. The method of claim 21 , wherein the neurodegenerative disease is Parkinson's disease.
35. The method of claim 21 , wherein the neurodegenerative disease is Alzheimer's disease.
36. The method of claim 21 , wherein the neurodegenerative disease is Amylotrophic Lateral Sclerosis.
37. The method of claim 21 , wherein the transferrin comprises an amino acid sequence with at least 80% identity to SEQ ID NO: 1.
38. The method of claim 21 , wherein the transferrin comprises an amino acid sequence with at least 90% identity to SEQ ID NO: 1.