Methods for treating inflammatory disorders and traumatic brain injury using stabilized non-hematopoietic epo short peptides

Abstract

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.

What is claimed is: 
     
         1 . A composition comprising an erythropoietin (EPO)-derived peptide, wherein the amino acid sequence of the EPO-derived peptide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 20, and SEQ ID NO: 30. 
     
     
         2 . The composition of  claim 1 , wherein the EPO-derived peptide is at least one of cyclic, non-hematopoietic, or both. 
     
     
         3 . The composition of  claim 1 , wherein the composition comprises a therapeutically effective amount of the EPO-derived peptide. 
     
     
         4 . The composition of  claim 1 , wherein the EPO-derived peptide includes a small bicyclic molecule on at least one of N-terminal end of the peptide, the C-terminal end of the peptide, or both. 
     
     
         5 . A method for limiting cognitive impairment in a subject suffering from an inflammatory disease of the brain or spinal cord comprising the steps of:
 (a) providing the composition of  claim 1 ; and   (b) administering to the subject a therapeutically effective amount of the composition, wherein the composition is effective for delaying progression of the inflammatory disease, thereby limiting cognitive impairment in the subject.   
     
     
         6 . The method according to  claim 5 , wherein the EPO-derived peptide is at least one of synthetic, non-hematopoietic, cyclic, or combinations thereof. 
     
     
         7 . The method according to  claim 5 , wherein the route of administering is selected from the group consisting of parenteral, oral, inhalation, insufflation, topical, buccal and rectal. 
     
     
         8 . The method according to  claim 5 , wherein the composition further comprises a pharmaceutically acceptable excipient. 
     
     
         9 . A method for prolonging survival of a subject suffering from an inflammatory disease of the brain or spinal cord comprising the steps of:
 (a) providing the composition of  claim 1 ; and   (b) administering to the subject a therapeutically effective amount of the composition, wherein the composition is effective for delaying the progression of the inflammatory disease, thereby prolonging survival of the subject.   
     
     
         10 . The method according to  claim 9 , wherein the EPO-derived peptide is at least one of synthetic, non-hematopoietic, cyclic, or combinations thereof. 
     
     
         11 . The method according to  claim 9 , wherein the route of administering is selected from the group consisting of parenteral, oral, inhalation, insufflation, topical, buccal and rectal. 
     
     
         12 . The method according to  claim 9 , wherein the composition further comprises a pharmaceutically acceptable excipient. 
     
     
         13 . A method of treating a disease, disorder or condition having an inflammatory or autoimmune component in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of  claim 1 , wherein the composition is effective at ameliorating at least one symptom from at least one disease, disorder, or condition having an inflammatory or autoimmune component. 
     
     
         14 . The method according to  claim 13 , wherein the EPO-derived peptide is at least one of synthetic, non-hematopoietic, cyclic, or combinations thereof. 
     
     
         15 . The method according to  claim 13 , wherein the non-hematopoietic biological activity of the EPO-derived peptide is stable when the peptide is stored at 4° C. 
     
     
         16 . The method according to  claim 13 , wherein the EPO-derived peptide is stabilized by at least one of:
 chemically adding a small bicyclic molecule to at least one of the N-terminal end or the C-terminal end of the peptide's amino acid sequence;   a disulfide bond formed between a sulfhydral group of a first amino acid residue and a sulfhydral group of a second amino acid residue along the peptide sequence; or   a combination thereof.   
     
     
         17 . The method according to  claim 16 , wherein the disease, disorder, or condition having an inflammatory or autoimmune component is selected from the group consisting of an acute cerebrovascular injury, an acute spinal cord injury, an acute brain injury, an acute cardiovascular injury, an arthritis, an autoimmune disease, a demyelinating disease, a stroke, multiple sclerosis, a neurological injury, and immune-mediated inflammation. 
     
     
         18 . The method according to  claim 13 , wherein the composition is administered by a route selected from the group consisting of orally, buccally, parenterally, nasally, rectally, and topically. 
     
     
         19 . The method according to  claim 13 , further comprising at least one of:
 monitoring the subject's red blood cell indices;   maintaining the subject's red cell indices at substantially normal levels during treatment or both.   
     
     
         20 . The method according to  claim 13 , wherein the EPO-derived peptide is at least one peptide whose amino acid sequence is SEQ ID NO: 7.