A Cystine-Rich Whey Supplement (Immunocal(®)) Delays Disease Onset and Prevents Spinal Cord Glutathione Depletion in the hSOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis

Depletion of the endogenous antioxidant, glutathione (GSH), underlies progression of the devastating neurodegenerative disease, amyotrophic lateral sclerosis (ALS). Thus, strategies aimed at elevating GSH may yield new therapeutics for ALS. Here, we investigated the effects of a unique non-denatured whey protein supplement, Immunocal(®), in the transgenic Gly position 93 to Ala (G93A) mutant hSOD1 (hSOD1(G93A)) mouse model of ALS. Immunocal(®) is rich in the GSH precursor, cystine, and is therefore capable of bolstering GSH content. Transgenic hSOD1(G93A) mice receiving Immunocal(®) displayed a significant delay in disease onset compared to untreated hSOD1(G93A) controls. Additionally, Immunocal(®) treatment significantly decreased the rate of decline in grip strength and prevented disease-associated reductions in whole blood and spinal cord tissue GSH levels in end-stage hSOD1(G93A) mice. However, Immunocal(®) did not extend survival, likely due to its inability to preserve the mitochondrial GSH pool in spinal cord. Combination treatment with Immunocal(®) and the anti-glutamatergic compound, riluzole, delayed disease onset and extended survival in hSOD1(G93A) mice. These findings demonstrate that sustaining tissue GSH with Immunocal(®) only modestly delays disease onset and slows the loss of skeletal muscle strength in hSOD1(G93A) mice. Moreover, the inability of Immunocal(®) to rescue mitochondrial GSH in spinal cord provides a possible mechanism for its lack of effect on survival and is a limiting factor in the potential utility of this supplement as a therapeutic for ALS.