The pharmaceutical industry has spent $200 million on drug trials for treating head trauma, all have failed, Identified problems include inappropriate selection of drug candidates, and failure to use prognostic indicators and surrogate biomarkers in clinical trials. Proposed Phase II studies assess the utility of our newly developed biomarker of neuronal damage as a surrogate biomarker and prognostic indicator in clinical drugs trials of neuroprotectant agents. Our Phase I studies developed a biomarker of neuronal damage. After head trauma, neuronal MAP-tau is proteolytically cleaved (C-tau) and gains access to cerebrospinal fluid (CSF) and serum where levels are elevated 30,000 fold and 300 fold respectively compared to controls. Further, patient C-tau levels were highly predictive of clinical outcome. Proposed Phase II studies will assess serial CSF and serum C-tau levels as surrogate biomarkers of clinical outcome in severe head injury patients (N=70). Serial CSF and serum C-tau levels will be measured at 24-hour periods after injury and their ability to predict patient outcome at 3 months determined (Specific Aims 2 and 4). The ability of initial CSF and serum C-tau levels to serve as screening biomarkers to identify head injured patients thought unlikely to respond to drug treatment (dead before end of study) will be determined and compared to the currently employed industry marker, initial Glasgow Coma Scores (N=70).
The C-tau ELISA will be utilized by the pharmaceutical industry in clinical drug trials as a purchased inhouse assay. Proposed Phase II studies put in place the foundation for a Phase III program which will develop our C-tau ELISA as an FDA approved in vitro diagnostic test for head trauma.
