Methods for detecting neurological disorders

Abstract

In one aspect, the present invention features methods for detecting at least one neurological disorder in a patient, the method comprising obtaining a biological sample from the patient; and detecting at least one aberrant human glutamate transporter 2 (EAAT 2) mRNA in the sample as being indicative of the neurological disorder in the patient. In a particular aspect, the invention is useful for detecting amyotrophic lateral sclerosis (ALS) in the patient.

1 . A method of detecting a neurological disorder in a patient, the method comprising obtaining a biological sample from the patient; and detecting at least one aberrant human glutamate transporter 2 (EAAT 2) mRNA in the sample as being indicative of the neurological disorder in the patient.  
     
     
         2 . The method of  claim 1 , wherein the neurological disorder is associated with excitotoxicity.  
     
     
         3 . The method of  claim 1 , wherein the neurological disorder affects motor neuron function.  
     
     
         4 . The method of  claim 1 , wherein the neurological disorder is amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Parkinson's disease (PD), or Alzheimer's disease (AD).  
     
     
         5 . The method of  claim 1 , wherein the sample comprises fluid obtained from the central nervous system (CNS) of the patient.  
     
     
         6 . The method of  claim 5 , wherein the fluid is cerebrospinal fluid (CSF).  
     
     
         7 . The method of  claim 1 , wherein the method further comprises amplifying the aberrant human glutamate transporter 2 (EAAT 2) mRNA by a polymerase chain reaction (PCR) sufficient to make cDNA from the mRNA.  
     
     
         8 . The method of  claim 7 , wherein the PCR is a reverse transcriptase-PCR reaction (RT-PCR).  
     
     
         9 . The method of  claim 7 , wherein the method further comprises determining a DNA sequence from the cDNA.  
     
     
         10 . The method of  claim 9 , wherein the DNA sequence is substantially homologous to a DNA sequence shown in any one of SEQ ID NOs. 3 and 5-13 or the complement thereof.  
     
     
         11 . The method of  claim 10 , wherein the DNA sequence is identical to any one of SEQ ID NOs. 3 and 5-13 or the complement thereof.  
     
     
         12 . The method of  claim 1 , wherein the method further comprises making a cDNA library from the sample, and detecting a cDNA in the library comprising DNA sequence substantially homologous to the aberrant human glutamate transporter 2 (EAAT 2) mRNA.  
     
     
         13 . The method of  claim 12 , wherein the DNA sequence of the cDNA is substantially homologous to any one of the SEQ ID NOs. 3 and 5-13 or the complement thereof.  
     
     
         14 . The method of  claim 12 , wherein the DNA sequence of the eDNA is identical to one of the SEQ ID Nos. 3 and 5-13 or the complement thereof.  
     
     
         15 . A method of isolating an aberrant human glutamate transporter 2 (EAAT 2) cDNA, the method comprising: 
 a) obtaining a biological sample from a patient having or suspected of having a neurological disorder, wherein the sample comprises mRNA,    b) producing cDNA from the sample, the cDNA comprising DNA sequence substantially homologous to any one of SEQ ID NOs. 3 and 5-13 or the complement thereof,    c) introducing the cDNA into test cells under conditions sufficient to express the cDNA in the test cells; and    d) detecting a reduction in glutamate transport in the test cells compared to control cells expressing a normal human glutamate transporter 2 gene or cDNA as indicative of isolation of the aberrant human glutamate transporter 2 (EAAT 2) cDNA.    
     
     
         16 . The method of  claim 15 , wherein the sample comprises nervous system tissue obtained from the patient.  
     
     
         17 . The method of  claim 15 , wherein the neurological disorder is associated with excitotoxicity.  
     
     
         18 . The method of  claim 15 , wherein the neurological disorder is a motor neuron disorder.  
     
     
         19 . The method of  claim 15 , wherein the neurological disorder is amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Parkinson's disease (PD), or Alzheimer's disease (AD).  
     
     
         20 . The method of  claim 15 , wherein the cDNA from the sample comprises sequence substantially homologous to the sequence of SEQ ID NOs. 3 and 5-13 or the complement thereof.