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Project

An 'Omics' Approach to Biomarker Discovery in Acute Human SCI

Funder: Craig H Neilsen Foundation

Funding period
USD 452 K
Funding amount
Abstract
Despite considerable scientific and clinical research efforts, there are currently no neuro-restorative treatments for acute SCI. This failure of translation has highlighted a number of challenges that impede the establishment of effective therapies for SCI. These include: 1. The paucity of information about the biology of human SCI, making it difficult to determine if injury responses so effectively targeted in rodents are indeed relevant to human SCI, 2) The lack of biomarkers to facilitate clinical trials which currently depend on functional outcome measures that are imprecise stratifiers of injury severity and 3) The lack of corresponding biological endpoints between animal models and humans. This project will be a bi-directional translational initiative that involves both clinical and preclinical investigations. In this proposal, we will: 1. Characterizing the temporal profile of genomic, proteomic and metabolomic changes within CSF and serum samples obtained from acute SCI patients, thereby providing an unprecedented breadth of biological information on the pathophysiology of human SCI; 2. Establishing biomarkers of injury severity and predictors of neurologic recovery by correlating these ‘-omic’ datasets with prospectively collected neurologic outcomes data; and 3. Conducting a parallel genomic, proteomic, and metabolomic analysis of CSF and serum samples from a porcine model of SCI to identify biologic commonalities and establish predictive biologic outcome measures for monitoring injury progression in both human and animal systems. We will take advantage of unique clinical and preclinical research assets. Firstly, on the clinical side, we are leading a prospective multi-center trial in which samples of CSF and blood from acute SCI patients are being collected and banked. Using ELISA techniques, we previously identified a small series of biomarkers of injury severity in CSF from acute SCI patients. We will now conduct a much broader interrogation of these samples through ‘-omic’ screening. The prospective recruitment of these patients ensures the accrual of high quality clinical outcomes data that are critical for establishing correlations with the biological data and identifying biomarkers of injury. On the preclinical side, we will perform a parallel biomarker discovery initiative using our pig model of SCI. The larger anatomy of the pig spinal cord and surrounding CSF space permits the serial collection of CSF with indwelling catheters in a manner similar to that in our human trial. We will therefore utilize the same ‘-omic’ platforms on CSF and serum samples obtained in our pig model of SCI. By determining similarities and differences with human SCI, we will generate a panel of markers that can be used both preclinical and clinical to evaluate biological responses to treatment. This could dramatically change the way that novel therapies are tested and then translated into early stage human clinical trials. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1103 Clinical Sciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Biotechnology

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Clinical Research

  • RCDC

    Neurodegenerative

  • HRCS RAC

    4.1 Discovery and preclinical testing of markers and technologies

  • Health Research Areas

    Clinical

  • Broad Research Areas

    Clinical Medicine and Science