Reduction in cerebral antioxidant, glutathione (GSH), in patients with ALS: A preliminary study (P6.105)

Abstract

OBJECTIVE: To assess whether glutathione (GSH), a major brain antioxidant, is lower in patients with amyotrophic lateral sclerosis (ALS) compared to matched controls. BACKGROUND: A reduction in GSH is noted in brain tissue samples undergoing cellular oxidative stress, which commonly accompanies many neurodegenerative diseases. We hypothesize that cerebral GSH loss may occur in ALS, where oxidative stress and associated cell death have been implicated. Moreover, GSH may serve as an in vivo biomarker linked to the underlying pathophysiology of ALS. DESIGN/METHODS: In this preliminary study, we studied 7 ALS patients who are relatively early in the disease course and 7 age/sex-matched controls between the ages of 52 and 72 in a cross-sectional study design. The patient enrollment criteria include El Escorial laboratory-supported possible or definite ALS, a vital capacity > 75[percnt], and symptom duration less than 2 years since disease onset. The neuroimaging protocol consisted of a novel MR chemical shift imaging of GSH at 3 Tesla. The concentrations of GSH were measured from an axial slice positioned in the frontal region superior to the lateral ventricles at the level of the motor cortex. We compared the two groups using two-tailed two-sample T-test. RESULTS: The mean frontal GSH concentration was 22[percnt] lower for ALS patients than healthy controls in the frontal region, mainly motor cortex areas (p=0.0005, n=7 for each group). Our finding of lower GSH in ALS is consistent with previous observation by Weiduschat and colleagues (Neurosci Lett. 2014) using the J-editing method. CONCLUSIONS: The lower brain GSH concentrations in ALS patients suggests ongoing oxidative stress and compromised endogenous antioxidant defenses. This oxidative process could be at least partially responsible for neuronal injury and functional decline in ALS. Study Supported by: The Amyotrophic Lateral Sclerosis Association and the National Institutes of Health (S10RR29577, UL1TR000001)

Disclosure: Dr. Choi has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Statland has nothing to disclose. Dr. McVey has nothing to disclose. Dr. Dimachkie has received personal compensation for activities with Pfizer, Depomed, Merck, CSL Behring, NuFACTOR, BioMarin Pharmaceutical, Baxter International, Inc., and Catalyst Pharmaceuticals as a consultant, speaker, and/or advisory board member. Dr. Brooks has nothing to disclose. Dr. Barohn has received personal compensation from Grifols, Genzyme, and NuFactor. Dr. Barohn has received personal compensation in an editorial capacity for Neurology Clinics of North America. Dr. Barohn has received research support from Cytokenetics.