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 - 14 . (canceled) 
     
     
         15 . A method of inhibiting the formation of membrane attack complex (MAC) in a subject diagnosed with a neurodegenerative disorder or physical injury of a nerve, comprising administering to the subject a therapeutically effective amount of an inhibitor of a mammalian complement system, wherein the inhibitor is an antisense oligonucleotide that binds to the mRNA sequence of human C5 or C6 of the complement system. 
     
     
         16 . The method according to  claim 15 , wherein the physical injury is of the peripheral or central nervous system. 
     
     
         17 . The method according to  claim 15 , wherein the neurodegenerative disorder is of the peripheral or central nervous system. 
     
     
         18 . The method according to  claim 15 , wherein the neurodegenerative disorder is Amyotrophic Lateral Sclerosis (ALS). 
     
     
         19 . The method of  claim 15 , wherein the antisense oligonucleotide is administered by an intradermal, intramuscular, intraperitoneal, intravenous, or subcutaneous route. 
     
     
         20 . The method according to  claim 15 , wherein the neurodegenerative disorder is Multiple Sclerosis (MS). 
     
     
         21 . (canceled) 
     
     
         22 . A method of promoting functional recovery of damaged or degenerating nerves in a subject by inhibiting the formation of membrane attack complex, comprising administering to the subject a therapeutically effective amount of an inhibitor of a mammalian complement system, wherein the inhibitor is an antisense oligonucleotide that binds to the mRNA sequence of human C5 or C6 of the complement system. 
     
     
         23 . The method of  claim 15  or  22 , wherein the antisense oligonucleotide is administered by an intradermal, intramuscular, intraperitoneal, intravenous, or subcutaneous route. 
     
     
         24 . The method of  claim 15  or  22  wherein the damaged or degenerating nerves are of the PNS or CNS. 
     
     
         25 . The method of  claim 15  or  22 , wherein the antisense oligonucleotide comprises one or more locked nucleic acids (LNA). 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 15  or  22 , wherein the antisense oligonucleotide comprises one or more peptide nucleic acids (PNA) or ethylene-bridged nucleotides (ENA). 
     
     
         28 . A method of inhibiting the formation of membrane attack complex (MAC) in a subject diagnosed with a neurodegenerative disorder or physical injury of a nerve, comprising administering to the subject a therapeutically effective amount of an inhibitor of a mammalian complement system, wherein the inhibitor is a complement receptor.