Innate Immune Proteins As Biomarkers for CNS Injury

Abstract

The present invention provides novel markers of the severity of a central nervous system injury, such as spinal cord injury or traumatic brain injury, in a patient. In particular, protein components of inflammasomes in the cerebrospinal fluid that can be used to assess the serverity of central nervous system injury in a patient are disclosed. Methods of using such protein biomarkers to determine a prognosis, direct treatment and rehabilition efforts, and monitor response to treatment for a patient with a central nervous system injury are also described.

1 .- 32 . (canceled) 
     
     
         33 . A method of treating a patient with a central nervous system (CNS) injury comprising administering a neuroprotective treatment to the patient with the central nervous system injury, wherein the patient comprises an elevated level of at least one inflammasome protein. 
     
     
         34 . The method of  claim 33 , wherein the elevated level of at least one inflammasome protein was measured in a biological sample obtained from the patient. 
     
     
         35 . The method of  claim 33 , wherein the elevated level of at least one inflammasome protein is relative to a pre-determined reference value or range of reference values. 
     
     
         36 . The method of  claim 35 , wherein the elevated level of at least one inflammasome protein relative to the pre-determined reference value or range of reference values is predictive of the patient having a Glasgow Outcome Scale (GOS) score of 1 to 3 upon follow-up assessment. 
     
     
         37 . The method of  claim 33 , wherein the neuroprotective treatment is hypothermia, methylprednisolone, 17α-estradiol, 17β-estradiol, ginsenoside, progesterone, simvastatin, deprenyl, minocycline, or resveratrol. 
     
     
         38 . The method of  claim 33 , wherein the neuroprotective treatment is a molecule that binds an inflammasome protein or epitope thereof. 
     
     
         39 . The method of  claim 38 , wherein the molecule specifically binds to SEQ ID NO: 1, 2, 3 or 4. 
     
     
         40 . The method of  claim 39 , wherein the molecule is an aptamer, antibody or binding fragment thereof. 
     
     
         41 . The method of  claim 34 , wherein the biological sample was obtained within a week of the suspected injury. 
     
     
         42 . The method of  claim 34 , wherein the biological sample was obtained within five days of the suspected injury. 
     
     
         43 . The method of  claim 34 , wherein the biological sample was obtained within three days of the suspected injury. 
     
     
         44 . The method of  claim 33 , wherein the at least one inflammasome protein is NLRP1, ASC, caspase-1, caspase-11, X-linked inhibitor of apoptosis protein (XIAP), pannexin-1 or combinations thereof. 
     
     
         45 . The method of  claim 44 , wherein the at least one inflammasome protein is the p20 subunit of caspase-1. 
     
     
         46 . The method of  claim 33 , wherein the CNS injury is a stroke-related injury, a spinal cord injury or traumatic brain injury. 
     
     
         47 . The method of  claim 34 , wherein the biological sample is CSF, CNS microdialysate, saliva, serum, plasma, or urine. 
     
     
         48 . The method of  claim 33 , wherein the level of the at least one inflammasome protein was measured by immunoblot or ELISA. 
     
     
         49 . The method of  claim 33 , wherein the patient is a pediatric patient.