Method of treatment of hypoxia inducible factor (HIF)-related conditions

Abstract

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.

The invention claimed is: 
     
       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, L1NA11, 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. 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, and wherein the transferrin is a mixture of apo-transferrin (Apo-Tf) and holo-transferrin (Holo-Tf) in a ratio from 99% Apo-Tf:1% Holo-Tf to 30% Apo-Tf:70% Holo-Tf.  
     
     
       15. The method of claim 14, wherein the neurodegenerative disease is Parkinson's disease.  
     
     
       16. The method of claim 14, wherein the neurodegenerative disease is Alzheimer's disease.  
     
     
       17. The method of claim 14, wherein the neurodegenerative disease is Amylotrophic Lateral Sclerosis.  
     
     
       18. The method of claim 14, wherein the composition further comprises an iron chelator or prolyl hydroxylase domain-containing protein 2 (PHD2) enzyme inhibitor.  
     
     
       19. The method of claim 18, wherein the iron chelator is selected from the group consisting of M30, deferoxamine (DFO), Deferasirox, deferiprone, deferitrin, L1NAII, CP363, CP502, and Ethylenediaminetetraacetic acid (EDTA).  
     
     
       20. The method of claim 18, wherein the PHD2 enzyme inhibitor is selected from the group consisting of IOX2, IOX3, and dimethyloxallylglycine.  
     
     
       21. The method of claim 14, wherein the transferrin is recombinant.  
     
     
       22. The method of claim 14, wherein the transferrin is modified by pegylation, glycosylation or polysialylation to extend its plasma half-life.