Complement inhibition for improved nerve regeneration

Abstract

The present invention relates to methods and medicaments used for treating conditions that require axonal regeneration, e.g. in mammals affected by injury or disease of the central or peripheral nervous system. The medicaments used in these methods facilitate axonal regeneration by inhibition of the complement system. Conditions requiring axonal regeneration that may be treated in accordance with the invention include physical injuries as well as neurodegenerative disorders of the peripheral or central nervous system.

1 . A method of treating a complement-related indication in a subject, comprising administering to the subject a peptide that inhibits C5 in an amount sufficient to treat the indication. 
     
     
         2 . A method of reducing hemolysis in a subject, comprising administering to the subject a peptide that inhibits C5 in an amount sufficient to reduce hemolysis. 
     
     
         3 . A method of inhibiting complement activation in a subject, comprising administering to the subject a peptide that inhibits C5 in an amount sufficient to inhibit complement activation. 
     
     
         4 . The method of any one of  claims 1 - 3 , wherein the peptide is cyclic. 
     
     
         5 . The method of any one of  claims 1 - 4 , wherein the peptide inhibits proteolytic cleavage of C5. 
     
     
         6 . The method of any one of  claims 1 - 5 , wherein the peptide binds to C5b and prevents assembly of C5b and C6. 
     
     
         7 . The method of any one of  claims 1 - 6 , wherein the peptide inhibits formation of membrane attack complex (MAC). 
     
     
         8 . The method of any one of  claims 1 - 7 , wherein the peptide inhibits activation of the alternative pathway of complement activation. 
     
     
         9 . The method of any one of  claims 1 - 7 , wherein the complement-related indication is an inflammatory indication, a wound, or an autoimmune indication. 
     
     
         10 . The method of any one of  claims 1 - 9 , wherein the peptide is in the form of a sustained release formulation. 
     
     
         11 . The method of any one of  claims 1 - 10 , wherein the peptide is administered by an intradermal, intramuscular, intraperitoneal, intravenous, or subcutaneous route. 
     
     
         12 . A cyclic peptide capable of inhibiting cleavage of C5 and assembly of C5b and C6. 
     
     
         13 . The peptide of  claim 12 , wherein the peptide inhibits formation of MAC. 
     
     
         14 . The peptide of  claim 12  or  13 , wherein the peptide inhibits activation of the alternative pathway of complement activation. 
     
     
         15 . A composition comprising the peptide of any one of  claims 12 - 14 . 
     
     
         16 . The composition of  claim 15 , wherein the composition is a sustained release formulation.