Biomarker detection process and assay of neurological condition

Abstract

The subject invention provides a robust, quantitative, and reproducible process and assay for diagnosis of a neurological condition in a subject. The invention provides measurement of two or more biomarkers in a biological fluid such as CSF or serum resulting in a synergistic mechanism for determining the extent of neurological damage in a subject with an abnormal neurological condition and for discerning subtypes thereof or tissue types subjected to damage.

1 . A process for determining the neurological condition of a subject or cells from the subject comprising:
 measuring a sample obtained from the subject or cells from the subject at a first time for a quantity of a first biomarker selected from the group of GFAP, UCH-L1, NSE, MAP2, S100b, or a SBDP, and a quantity of at least one additional neuroactive biomarker; and   comparing the quantity of said first biomarker and the quantity of said at least one additional neuroactive biomarker to normal levels of said first biomarker and said at least one additional neuroactive biomarker to determine the neurological condition of the subject.   
     
     
         2 . The process of  claim 1  wherein the sample is cerebrospinal fluid or blood serum. 
     
     
         3 . The process of  claim 1  wherein the sample is a culture of the cells exposed to a drug candidate or an environmental contaminant. 
     
     
         4 . The process of  claim 1  wherein said at least one additional neuroactive biomarker is GFAP, UCH-L1, NSE, SBDP150, SBDP145, SBDP120, S100b, MAP2, MAP1, MAP3, MAP4, MAP5, MBP, Tau, Neurofilament protein (NF), Cannabinoid Receptor CB, CAM, Synaptic protein, CRMP, iNOS, NeuN, CNPase, Neuroserpin, alpha-internexin, LC3, Neurofascin, EAAT, Nestin, Cortin-1, or BIII-Tubulin. 
     
     
         5 . The process of  claim 1  wherein is at least one additional neuroactive biomarker is one of GFAP, UCH-L1, NSE, SBDP150, SBDP150i, SBDP145, SBDP120, or MAP2. 
     
     
         6 . The process of  claim 1  further comprising measuring a second quantity of said first biomarker and a second quantity of said at least one additional neuroactive biomarker at a second time to yield a kinetic profile for said first biomarker and said at least one additional neuroactive biomarker. 
     
     
         7 . The process of  claim 1  further comprising comparing the quantity of said first biomarker and the quantity of said at least one additional neuroactive biomarker between normal levels in the subject to other individuals of the same gender as the subject. 
     
     
         8 . The process of  claim 1  wherein said at least one additional neuroactive biomarker is GFAP. 
     
     
         9 . The process of  claim 7  wherein said first biomarker is UCH-L1 and determined if the subject or cells from the subject has been exposed to some degree of traumatic brain injury ranging from mild to severe. 
     
     
         10 . The process of  claim 9  further comprising predicting mortality based on the quantity of UCH-L1 and the quantity of GFAP. 
     
     
         11 . The process of  claim 9  wherein mild traumatic brain injury and moderate traumatic brain injury have detection cutoffs for UCH-L1 and GFAP in serum of 0.39 ng/ml and 1.4 ng/ml, respectively. 
     
     
         12 . The process of  claim 1  wherein the at least one additional neuroactive biomarker is S100b. 
     
     
         13 . The process of  claim 1  wherein the at least one additional neuroactive biomarker is a SBDP of SBDP150, SBDP150i, SBDP145, or SBDP120. 
     
     
         14 . The process of  claim 1  wherein the at least one additional neuroactive biomarker is NSE. 
     
     
         15 . The process of  claim 1  wherein the at least one additional neuroactive biomarker is a MAP of MAP2, MAP1, MAP3, MAP4, or MAP5.