Methods for monitoring neuroinflammatory destruction of neurons and for treating diseases having an inflammatory component related to phospholipase a2

Abstract

The present invention relates to methods useful to monitor central and peripheral nervous system neuron/axon destruction resulting from an increase in acute phase inflammatory enzymes. The methods have applicability to monitoring the progress of neurological diseases, including multiple sclerosis and Alzheimer's disease, as well as neuroinflammatory damage that results from sports injuries, vigorous physical activity or any form of physical abuse. The invention further relates to methods of treating multiple sclerosis or other diseases with an inflammatory component related to phospholipase A2.

1 .- 16 . (canceled) 
     
     
         17 . A method of monitoring progression of multiple sclerosis (MS in a mammal, said method comprising:
 a. taking a first measurement of secreted phospholipase A2 (PLA2) activity in a first urine sample obtained from said mammal;   b. taking a second measurement of PLA2 activity in a second urine sample obtained from said mammal, wherein said second sample is obtained at a later time than said first sample; and   c. comparing said first and second measurements, wherein a second measurement larger than said first measurement is an indication that the MS is progressing in said mammal.   
     
     
         18 .- 20 . (canceled) 
     
     
         21 . A method of monitoring progression of an inflammatory condition in a mammal, said method comprising:
 a. taking a first measurement of secreted phospholipase A2 (PLA2) activity in a first urine sample obtained from said mammal;   b. taking a second measurement of PLA2 activity in a second urine sample obtained from said mammal, wherein said second sample is obtained at a later time than said first sample; and   c. comparing said first and second measurements, wherein a second measurement larger than said first measurement is an indication that the inflammatory condition is progressing in said mammal.   
     
     
         22 . The method of  claim 21 , wherein taking first and second measurements further comprises reacting the first and second urine samples with a PLA2 substrate. 
     
     
         23 . The method of  claim 22 , wherein the PLA2 substrate is selected from the group consisting of 1-palmitoyl-2-pyrenedecanoyl phosphatidylcholine, thio-glycerophosphocholine and 1,2-bis(heptanoylthio) glycerophosphocholine. 
     
     
         24 . The method of  claim 22 , wherein taking first and second measurements further comprises measuring PLA2 cleavage of the PLA2 substrate. 
     
     
         25 . The method of  claim 21 , wherein the PLA2 activity measurements detect PLA2 enzymatic activity. 
     
     
         26 . The method of  claim 25 , wherein the enzymatic activity is detected with a fluorescent PLA2 substrate. 
     
     
         27 . The method of  claim 21  further comprising detecting at least a fragment of at least one nervous system-specific protein in the first and second urine samples. 
     
     
         28 . The method of  claim 27 , wherein the nervous system-specific protein is detected with an antibody-based assay. 
     
     
         29 . The method of  claim 27 , wherein the nervous system-specific protein is selected from the group consisting of neurofilament protein, beta tubulin isotype III, oligodendrocyte specific protein, glial fibrillary acidic protein, myelin basic protein, NeuN, and combinations thereof.