POD 1

NMR Metabolomics of Cerebrospinal Fluid and Urine for Accelerated Diagnosis of Pediatric Encephalomyelitis

This project addresses the challenge that standard medical practice for encephalomyelitis is limited while outcomes are often poor, including death or permanent disability. Our project is very high impact given (a) the critical importance of neurological function to quality of life, (b) the change-making paradigm shift of diagnosing and treating encephalomyelitis by profiling brain metabolism, and (c) the practicality of immediate translation of our research into clinical practice. The research is highly collaborative, nucleating strategically focused CTSA teams at the Medical College of Wisconsin, New York University, University of Alabama (Birmingham), University of Cincinnati, and University of Massachusetts. This translational project is well matched to the missions of the respective Departments of Pediatrics, their CTSAs and the NIH, including NIAID, NINDS, NIAMS and NCI.

Our research delivers improved diagnostic speed, broader diagnostic range, and a theoretical framework that potentially identifies novel therapies. In our hands, nuclear magnetic resonance (NMR) metabolomics differentiates rabies, West Nile and Lyme encephalitis, cerebral malaria, multiple sclerosis and controls, and can likely do so for other brain diseases. The assay is rapid, cheap, ubiquitous, commercially adaptable and consumes less volume of CSF than current practices.

POD 1 proposes to prospectively enroll at least 15 children at each institution (75 total) with possible meningoencephalitis. Cerebrospinal fluids and concomitant urine samples will be analyzed by NMR. Metabolites will be identified and quantified by Chenomx software. Metabolic profiles will be clustered, distances between clusters compared, and correlations with clinical diagnoses reported. Study protocols will include sample collection and archiving for next generation sequencing, lateral flow assays, and proxy measures of treatment effects by CHAMP members.

7
A Novel Proteomic Approach to the Diagnosis of Pediatric Encephalomyelitis