Glutathione in Parkinson's disease

Thesis (Ph.D.)--University of Washington, 2016-03

Parkinson’s Disease (PD) is one of several prevalent neurodegenerative diseases plaguing the aging population. To date, no therapies have been shown to slow, stop, or reverse disease progression; the disease is considered irreversible and progressive. Post mortem brain from individuals with premotor PD show a deficiency of reduced glutathione, GSH, and it has been hypothesized that deficiency of GSH contributes to PD neurodegeneration. The role of GSH in the healthy brain is described, and evidence of GSH deficiency in PD is reviewed. The pros and cons of various augmentation strategies are discussed. Subsequent chapters demonstrate intranasal GSH, (in)GSH, is safe and tolerable and provide evidence that 200 mg (in)GSH is capable of augmenting brain GSH by more than 200%. In congruence with intravenous GSH studies, (in)GSH intervention groups had a mild symptomatic improvement following three months of (in)GSH administration. In a cross-sectional analysis of 58 individuals with PD, low blood GSH was associated with greater disease severity. Taken together, this body of research supports the hypothesis that GSH depletion contributes to PD and that (in)GSH has therapeutic potential as both a symptomatic treatment and a disease modification strategy. The final chapter describes an underlying GSH deficiency syndrome, with elderly, sick, and/or malnourished individuals at greatest risk. Sufficient data exists to warrant further investigation of GSH as a biomarker and (in)GSH as a disease-modifying therapy in PD.