Introduction
Multiple sclerosis (MS) is a chronic disorder of the central nervous system that leads to demyelination and neurodegeneration. Disease modifying drugs can minimize relapses and the concomitant mostly reversible neurological deficits in the inflammation-driven relapsing-remitting phase. To date, however, no treatment exists to preclude disability and functional decline in the secondary progressive phase. Despite enormous research progress, the cause of MS and the underlying neurobiological mechanisms remain poorly understood, thereby preventing improved treatment or the development of a true cure. Magnetic resonance spectroscopy (MRS) allows to assess the pathological changes and brain damage from the earliest stage and to monitor disease progression.
Goal
Our goal is to provide crucial tools to obtain information early in the development of MS disability, diagnostic biomarkers for early identification, and direct knowledge concerning pathophysiological mechanisms.
Current Work
Previous MRS studies focused on structural and cellular integrity and, therefore mainly aimed to quantify the neurochemicals N-acetyl-aspartate (NAA), choline and myo-inositol. Recent research has started to shed light on the relevance of certain neurochemicals for the pathological processes themselves. Largely based on in vitroinvestigations and animal models it has been hypothesized that dysfunction of the glutathione (GSH) metabolism impairs the brain's auto-protection against oxidative stress, thereby promoting demyelination, neurotoxicity and cell death as basis for functional decline in MS. However, to what extent the neurochemistry of GSH is deficient in MS remains unknown, in part due to constraints to non-invasively measure GSH in clinical populations and healthy controls in vivo.
We recently demonstrated the quantification of GSH along with other key players of MS (glutamate, GABA), established biomarkers of MS (NAA, choline, myo-inositol) and the overall biochemical environment in a single 1-hour session (Prinsen et al, Proc ISMRM, 2014). We expect this metabolomics-type approach to provide crucial insights in the role of GSH metabolism in MS and to set the stage for longitudinal clinical studies targeting the pathobiochemistry of oxidative stress.