Treating neurological disorders

Abstract

Methods of treating neuronal disorders, such as mechanical neuronal traumas and neurodegenerative disorders, with TWEAK or TWEAK-R blocking agents are presented.

1 . A method for treating a human subject who has or is at risk for a neurological disorder selected from the group consisting of a spinal cord injury, a traumatic brain injury, amyotropic lateral sclerosis (ALS), Parkinson's Disease, Huntington's Disease, and Alzheimer's Disease, the method comprising:
 administering to the subject an agent that blocks a TWEAK/TWEAK-R interaction or activity, wherein the agent is an antibody or a soluble form of a TWEAK receptor.   
   
   
       2 . The method of  claim 1  wherein the agent reduces the ability of TWEAK to bind to Fn14. 
   
   
       3 . The method of  claim 2  wherein the agent is an antibody that binds to TWEAK. 
   
   
       4 . The method of  claim 2  wherein the agent is an antibody that binds to Fn14. 
   
   
       5 . The method of  claim 3  or  4  wherein the antibody is a full-length IgG. 
   
   
       6 . The method of  claim 3  or  4  wherein the antibody consists of an antigen binding fragment of an IgG. 
   
   
       7 . The method of  claim 3  or  4  wherein the antibody is a human or humanized antibody. 
   
   
       8 . The method of  claim 2  wherein the agent is a soluble form of a TWEAK receptor. 
   
   
       9 . The method of  claim 8  wherein the soluble form of the TWEAK receptor is fused with an antibody Fc region. 
   
   
       10 . The method of  claim 1  wherein the agent is administered in an amount or for a time sufficient to reduce the amount of neuronal cell death in the subject. 
   
   
       11 . The method of  claim 1  wherein the agent is administered in an amount or for a time sufficient to reduce the amount of neuronal cell death in the subject, relative to a similarly affected, but untreated subject. 
   
   
       12 . The method of  claim 1  wherein the neurological disorder is a spinal cord injury or a traumatic brain injury, and wherein the subject has experienced the spinal cord injury within the previous 48 hours. 
   
   
       13 . The method of  claim 1  wherein the agent is administered in combination with another treatment for the neurological disorder. 
   
   
       14 . The method of  claim 13 , wherein the neurological disorder is a spinal cord injury, and wherein the other treatment comprises administering corticosteroids such as methylprednisolone or stabilization of the vertebrae of the spine. 
   
   
       15 - 90 . (canceled) 
   
   
       91 . The method of  claim 13 , wherein the neurological disorder is a traumatic brain injury, and wherein the other treatment comprises surgery to control bleeding in and around the brain, monitoring and controlling intracranial pressure, insuring adequate blood flow to the brain, or treating the body for other injuries and infection. 
   
   
       92 . The method of  claim 13 , wherein the neurological disorder is ALS, and wherein the other treatment comprises administering riluzole. 
   
   
       93 . The method of  claim 13 , wherein the neurological disorder is Parkinson's Disease, and wherein the other treatment comprises administering levodopa, a dopamine agonist, or an MAO-B inhibitor. 
   
   
       94 . The method of  claim 13 , wherein the neurological disorder is Huntington's Disease, and wherein the other treatment comprises administering bromocriptine, a serotonin antagonist, tiapride, or a NMDA receptor blocker. 
   
   
       95 . The method of  claim 13 , wherein the neurological disorder is Alzheimer's Disease, and wherein the other treatment comprises administering tacrine (COGNEX®), donepezil (ARICEPT®), rivastigmine (EXELON®)), galantamine (REMINYL®), memantine (NAMEND A™), a nonsteroidal anti-inflammatory drug (NSAID), a statin, folic acid, gingko biloba, or vitamin E, B6, or B12. 
   
   
       96 . The method of  claim 1 , wherein the subject has been diagnosed as having symptoms of the neurological disorder or a predisposition to the developing the neurological disorder, wherein the neurological disorder is Huntington's Disease or Alzheimer's Disease. 
   
   
       97 . The method of  claim 1 , further comprising: evaluating the subject using an assessment criterion specific for the neurological disorder. 
   
   
       98 . A method comprising: identifying a subject who has or is at risk for a neurological disorder selected from the group consisting of a spinal cord injury, a traumatic brain injury, amyotropic lateral sclerosis (ALS), Parkinson's Disease, Huntington's Disease, and Alzheimer's Disease; and administering to the subject an agent that blocks a TWEAK/TWEAK-R interaction or activity. 
   
   
       99 . A method comprising: detecting in a subject a neurological disorder selected from the group consisting of a recent spinal cord injury, a recent traumatic brain injury, amyotropic lateral sclerosis (ALS), Parkinson's Disease, Huntington's Disease, and Alzheimer's Disease; and administering to the subject an agent that blocks a TWEAK/TWEAK-R interaction or activity. 
   
   
       100 . A container comprising: an agent that blocks a TWEAK/TWEAK-R interaction or activity; and a label with instructions for use of the agent in treating a neurological disorder selected from the group consisting of a spinal cord injury, a recent traumatic brain injury, amyotropic lateral sclerosis (ALS), Parkinson's Disease, Huntington's Disease, and Alzheimer's Disease.