A randomized, double-blind phase I/IIa study of intranasal glutathione in Parkinson's disease

Abstract

Background Depletion of reduced glutathione is associated with Parkinson’s disease (PD) and glutathione augmentation has been proposed as a disease-modifying strategy. Objectives The purpose of this study was to determine the safety and tolerability of intranasal reduced glutathione in individuals with PD. Methods 30 individuals with PD were randomized to either placebo (saline), 300 mg/day or 600 mg/day intranasal glutathione in 3 divided daily doses. Follow-up visits included side effect screening of PD symptoms and cognition, blood chemistry, sinus irritation, and hyposmia. Tolerability was measured by frequency and severity of reported adverse events, compliance and withdrawals from the study. Results After 3 months, there were no substantial differences between groups in the number of adverse events reported or observed among all safety measures assessed. All groups met tolerability criteria. Conclusions These data support the safety and tolerability of intranasal glutathione in this population. Pharmacokinetic and dose-finding studies are warranted.

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

“…The decline of glutathione levels in Alzheimer's patient was associated with downregulation of glutathione homeostasis (Braidy et al, 2015 ). Parkinson's patients suffer depletion of glutathione levels coupled with an increase of ROS within the midbrain (Mischley et al, 2015 ). Removal of ROS by glutathione can facilitate the regulation of redox potential of the midbrain.…”

Nexus between mitochondrial function, iron, copper and glutathione in Parkinson's disease

“…Depletion of glutathione from rat brain substantia nigra is sufficient to induce dopaminergic neuron death and motor impairment (Garrido et al, 2011). Three small phase I/II clinical trials assessing glutathione delivery to PD patients have produced mild yet positive results (Hauser et al, 2009;Mischley et al, 2015;Sechi et al, 1996). Hence loss of glutathione per se is sufficient to kill substantia nigra neurons, and therapeutic rescue of glutathione levels may provide clinical benefit.…”

Is Modulation of Oxidative Stress an Answer? The State of the Art of Redox Therapeutic Actions in Neurodegenerative Diseases

“…Initial results seem to document additive neuroprotective effects in terms of significant reduction of DA depletion in the striatum and loss of tyrosine hydroxylase neurons in the SNpc, as well as reduction in lipid peroxidation and pathologic accumulation of α -synuclein in the same SNpc neurons [ 26 ]. Further, a double blind phase I/IIa clinical study proved the safety and tolerability of intranasal GSH administration to early and untreated patients, although pharmacokinetic and dose-finding investigations still need to be verified [ 27 ]. As already described for AD, another potential therapeutic strategy lies in the modulation of heavy metals, whereby the control of their bioavailability could prevent not only the increase of oxidative stress through metalloredox reactions, but also their interaction with other proteins like α -synuclein.…”