Method of Treating Peripheral Nerve Disorders

Abstract

The invention relates to the use of agents that bind the complement protein C5 in the treatment of diseases associated with inappropriate complement activation, and in particular in the treatment of peripheral nerve disorders.

1 . A method of treating or preventing a peripheral nerve disorder comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of an agent that binds complement C5. 
     
     
         2 . Use of a therapeutically or prophylactically effective amount of an agent that binds complement C5 in the manufacture of a medicament for treating or preventing a peripheral nerve disorder. 
     
     
         3 . A method according to  claim 1  or use according to  claim 2  wherein the agent acts to prevent the cleavage of complement C5 by C5 convertase into complement C5a and complement C5b-9. 
     
     
         4 . A method or use according to any one of  claims 1  to  3  wherein the agent binds C5 with an IC 50  of less than 0.2 mg/ml. 
     
     
         5 . A method or use according to any one of  claims 1  to  4  wherein the agent is derived from a haematophagous arthropod. 
     
     
         6 . A method or use according to any one of  claims 1  to  5  wherein the agent that binds C5 is a protein comprising or consisting of amino acids 19 to 168 of the amino acid sequence in  FIG. 2  or is a functional equivalent of this protein. 
     
     
         7 . A method or use according to any one of  claims 1  to  5  wherein the agent that binds C5 is a protein comprising or consisting of amino acids 1 to 168 of the amino acid sequence in  FIG. 2  or is a functional equivalent of this protein. 
     
     
         8 . A method or use according to any one of  claims 1  to  5  wherein the agent is a nucleic acid molecule encoding a protein as recited in  claim 6  or  7 . 
     
     
         9 . A method or use according to  claim 8  wherein the nucleic acid molecule comprises or consists of bases 53 to 507 of the nucleotide sequence in  FIG. 2 . 
     
     
         10 . A method or use according to  claim 9  wherein the nucleic acid molecule comprises or consists of bases 1 to 507 of the nucleotide sequence in  FIG. 2 . 
     
     
         11 . A method or use according to any one of  claims 1  to  10  wherein the subject is a mammal, preferably a human. 
     
     
         12 . A method or use according to any one of  claims 1  to  10  wherein the agent is administered in a dose sufficient to bind as much available C5 as possible in the subject, more preferably, all available C5. 
     
     
         13 . A method or use according to any one of  claims 1  to  12  wherein the agent is administered intravenously at a dose of 13 mg/kg followed by a 12-hourly dose of 4 mg/kg intraperitoneally. 
     
     
         14 . A method or use according to any one of  claims 1  to  13  wherein the agent that binds C5 is administered as part of a treatment regimen also involving the administration of a further drug for the treatment of a peripheral nerve disorder. 
     
     
         15 . A method of use according to  claim 14  wherein the further drug is immunoglobulin. 
     
     
         16 . A method of use according to  claim 14  or  claim 15  wherein the agent that binds C5 is administered simultaneously, sequentially or separately with the further drug. 
     
     
         17 . A method or use according to any one of  claims 1  to  16  wherein the peripheral nerve disorder is selected from the group consisting of post-infective demyelinating polyradiculoneuropathy (Guillain Barré syndrome), Miller Fisher syndrome, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), diabetic neuropathy, uraemic pruritus, multifocal motor neuropathy, paraproteinaemic neuropathy, anti-Hu neuropathy, post-diphtheria demyelinating neuropathy, multiple sclerosis, radiation myelopathy, giant cell arteritis (temporal arteritis), transverse myelitis, motor neurone disease, dermatomyositis. 
     
     
         18 . A method or use according to  claim 17  wherein the peripheral nerve disorder is selected from the group consisting of Guillain Barré Syndrome, chronic inflammatory demyelinating polyradiculoneuropathy.