Methods of treating dementia using a gm-csf antagonist

Abstract

The invention is based on the discovery that GM-CSF antagonists can be used for the treatment of a patient that has Alzheimer's disease or vascular dementia, or is at risk for developing Alzheimer's disease. Accordingly, the invention provides methods of administering a GM-CSF antagonist, e.g., a GM-CSF antibody and pharmaceutical compositions comprising such antagonists.

What is claimed is: 
     
         1 . A method for treating a patient suffering from vascular dementia or cerebral amyloid angiopathy, the method comprising administering a recombinant GM-CSF antagonist to the patient, wherein the recombinant GM-CSF antagonist is provided in a therapeutically effective amount. 
     
     
         2 . The method of  claim 1 , wherein the recombinant GM-CSF antagonist is provided in an amount to prevent cognitive decline. 
     
     
         3 . The method of  claim 1 , wherein the patient has mild cognitive impairment. 
     
     
         4 . The method of  claim 1 , wherein the patient has cerebral amyloid angiopathy. 
     
     
         5 . The method of  claim 1 , wherein the patient has elevated levels of GM-CSF in the cerebrospinal fluid (CSF) or serum, or both CSF and serum. 
     
     
         6 . The method of  claim 1 , wherein the recombinant GM-CSF antagonist is administered using intrathecal or perispinal administration. 
     
     
         7 . The method of  claim 1 , wherein the recombinant GM-CSF antagonist is a neutralizing anti-GM-CSF antibody 
     
     
         8 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody is an antibody fragment that is a Fab, a Fab′, a F(ab′) 2 , a scFv, or a dAB. 
     
     
         9 . The method of  claim 8 , wherein the antibody fragment is conjugated to polyethylene glycol. 
     
     
         10 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody has a K D  of less than 100 pM. 
     
     
         11 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody is a chimeric antibody. 
     
     
         12 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody is a human antibody. 
     
     
         13 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody comprises a human variable region. 
     
     
         14 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody comprises a human light chain constant region and/or a human heavy chain constant region. 
     
     
         15 . The method of  claim 14 , wherein the human heavy chain constant region is a gamma subclass. 
     
     
         16 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody binds to the same epitope as chimeric 19/2. 
     
     
         17 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody comprises a heavy chain variable (V H ) region having the sequence of SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:13. 
     
     
         18 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody comprises a light chain variable (V L ) region having the sequence of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, or SEQ ID NO:18. 
     
     
         19 . The method of  claim 7 , wherein the neutralizing anti-GM-CSF antibody comprises a V H  region having the sequence of SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:13; and a V L  region having the sequence of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, or SEQ ID NO:18.