BIOMARKER OF NEUROTOXICITY IN MENINGITIS
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.
Small Business Information at Submission:
Business Contact:James Hillard
PHASE 2 DISCOVERY, INC.
PHASE 2 DISCOVERY, INC. 3130 HIGHLAND AVE, 3RD FL CINCINNATI, OH 45219
Number of Employees: