Prognostic and Diagnostic Glycan-Based Biomarkers of Brain Damage

Abstract

The present disclosure relates to glycan-based biomarkers for the diagnosis or prognosis of brain damage, such as traumatic brain injury (TBI).

1 - 8 . (canceled) 
     
     
         9 . A method of determining therapeutic efficacy of a pharmaceutical drug in a subject with a brain injury, the method comprising steps of:
 administering a pharmaceutical drug to a subject with a brain injury;   contacting samples taken from the subject at two or more time points with a lectin array, wherein the samples are urine or saliva samples;   determining the level of glycan in the samples bound to at least one lectin in the lectin array, wherein the at least one lectin is  Galanthus nivalis  (GNA),  Allium sativum  (ASA),  Narcissus pseudo narcissus  (NPA),  Pisum sativum  (PSA),  Datura stramonium  (DSA), Leucoagglutinin (PHA-L),  Sambucus nigra  (SNA-I) or  Hippeastrum hybrid  (HHA);   detecting a change in the determined levels of said glycan bound to the at least one lectin during the course of administration of the pharmaceutical drug; and   identifying efficacy of the drug from the change in the level of the glycan bound to the at least one lectin, wherein the drug is identified as ineffective when the amount or relative amount of one or more of the glycans does not change toward the amount or relative amount of the glycan of a non-brain injury control; and the drug is identified as effective when the amount of one or more glycans change toward the amount or relative amount of the one or more glycans of a non-brain injury control.   
     
     
         10 . The method of  claim 9  that comprises detecting a change in the amount or relative amount of said glycan bound to the at least one lectin toward the amount or relative amount of the glycan of a non-brain injury control during the course of administration of the pharmaceutical drug; and
 identifying the pharmaceutical drug as an effective drug from the change in the amount or relative amount of the glycan bound to the at least one lectin. 
 
     
     
         11 . The method according to  claim 10 , wherein said brain injury is selected from the group consisting of traumatic brain injury (TBI), mild TBI, severe TBI, or acquired brain injury (ABI). 
     
     
         12 . The method according to  claim 11 , wherein said traumatic brain injury is a concussion. 
     
     
         13 . The method according to  claim 10 , wherein said determining the level of glycan further comprises using mass spectrometry, electrophoresis, a chromatographic method, an enzyme assay, a binding assay, or a combination thereof. 
     
     
         14 . The method according to  claim 13 , wherein said determining the level of glycan further comprises using MALDI-TOF mass spectrometry. 
     
     
         15 . A method of treating a subject known or suspected of having a brain injury, the method comprising:
 (a) administering a pharmaceutical drug to a subject with a brain injury; and   (b) monitoring the subject by:
 contacting samples taken from the subject at two or more time points with a lectin array, wherein the samples are urine or saliva samples; and 
 determining the level of glycan in the samples bound to at least one lectin in the lectin array, wherein the at least one lectin is  Galanthus nivalis  (GNA),  Allium sativum  (ASA),  Narcissus pseudo narcissus  (NPA),  Pisum sativum  (PSA),  Datura stramonium  (DSA), Leucoagglutinin (PHA-L),  Sambucus nigra  (SNA-I) or  Hippeastrum hybrid  (HHA); 
   wherein the administering comprises multiple doses of the pharmaceutical drug over time, to achieve a change in the amount or relative amount of the glycan bound to the at least one lectin toward the amount or relative amount of the glycan of a non-brain injury control, as determined by said monitoring of the subject.   
     
     
         16 . The method according to  claim 15 , wherein said brain injury is selected from the group consisting of traumatic brain injury (TBI), mild TBI, severe TBI, or acquired brain injury (ABI). 
     
     
         17 . The method according to  claim 16 , wherein said traumatic brain injury is a concussion. 
     
     
         18 . The method according to  claim 15 , wherein said determining further comprises using mass spectrometry, electrophoresis, a chromatographic method, an enzyme assay, a binding assay, or a combination thereof. 
     
     
         19 . The method according to  claim 18 , wherein said determining further comprises using MALDI-TOF mass spectrometry. 
     
     
         20 . A method of treating a subject known or suspected of having a brain injury, the method comprising:
 (a) administering a pharmaceutical drug to a subject with a brain injury, wherein the administering comprises multiple doses of the pharmaceutical drug over time;   (b) monitoring the efficacy of the treatment of the subject with the pharmaceutical drug by:
 contacting samples taken from the subject at two or more time points with a lectin array, wherein the samples are urine or saliva samples; and 
 determining the level of glycan in the samples bound to at least one lectin in the lectin array, wherein the at least one lectin is  Galanthus nivalis  (GNA),  Allium sativum  (ASA),  Narcissus pseudo narcissus  (NPA),  Pisum sativum  (PSA),  Datura stramonium  (DSA), Leucoagglutinin (PHA-L),  Sambucus nigra  (SNA-I) or  Hippeastrum hybrid  (HHA); and 
   (c) adjusting the dose or dosing of the pharmaceutical drug to achieve a change in the amount or relative amount of the glycan toward the amount or relative amount of the glycan of a non-brain injury control.   
     
     
         21 . The method according to  claim 20 , wherein said brain injury is selected from the group consisting of traumatic brain injury (TBI), mild TBI, severe TBI, or acquired brain injury (ABI). 
     
     
         22 . The method according to  claim 21 , wherein said traumatic brain injury is a concussion. 
     
     
         23 . The method according to  claim 20 , wherein said determining further comprises using mass spectrometry, electrophoresis, a chromatographic method, an enzyme assay, a binding assay, or a combination thereof. 
     
     
         24 . The method according to  claim 23 , wherein said determining further comprises using MALDI-TOF mass spectrometry.