BIOMARKER OF NEUROTOXICITY IN MENINGITIS

Award Information
Agency:
Department of Health and Human Services
Amount:
$112,627.00
Program:
SBIR
Contract:
1R43NS043013-01
Solitcitation Year:
N/A
Solicitation Number:
N/A
Branch:
N/A
Award Year:
2002
Phase:
Phase I
Agency Tracking Number:
NS043013
Solicitation Topic Code:
N/A
Small Business Information
PHASE 2 DISCOVERY, INC.
PHASE 2 DISCOVERY, INC., 3130 HIGHLAND AVE, 3RD FL, CINCINNATI, OH, 45219
Hubzone Owned:
N
Woman Owned:
N
Socially and Economically Disadvantaged:
N
Duns:
N/A
Principal Investigator
 JAMES MULCHAHEY
 (513) 475-7718
 JMULCHAHEY@PHASE2D.COM
Business Contact
 JAMES HILLARD
Phone: (513) 558-4274
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): The objective of this Phase I application is to develop a sensitive biomarker for quantifying neurotoxicity and neuroprotectant efficacy in meningitis. Previous research documents that brain injury caused by meningitis affects multiple brain areas with a heterogeneous distribution. We have previously shown that the cytoskeletal protein MAP-tau is cleavedin brain during axonal degeneration. We developed a sensitive ELISA that specifically quantifies this biomarker of neuronal degeneration, cleaved-tau (C-tau). Our preliminary studies demonstrate that levels of C-tau are increased over 300-fold in an animal model of group B streptococcus meningitis (GBM). We will use the well-documented neurotoxicity of GBM to validate the C-tau as a biomarker of neurotoxicity and a measure of neuroprotectant efficacy. Our Specific Aims are: Specific Aim 1: Determine whether GBM results in a time-dependent elevation in brain, plasma and CSF concentrations of C-tau. Specific Aim 2: Determine it C-tau levels in brain, CSF and plasma correlate with traditional measures of neuronal damage in GBM. Specific Aim 3: Determine whether perihperal tissues such as liver, kidney or spleen are potential sources of C-tau measured in GBM. Specific Aim 4: Determine whether a neuroprotectant intervention known to be effective in GBM has predictable effects on C-tau levels. PROPOSED COMMERCIAL APPLICATIONS: The C-tau ELISA may be used to quantify the severity of brain injury in meningitis and to quantify the effects of neuroprotectant interventions in basic science, preclinical and clinical research settings.

* information listed above is at the time of submission.

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