Glutathione 

Deficiency 

in 

Parkinson’s 

 Disease: Intranasal Administration as a Method of Augmentation

Reduced glutathione (GSH) is a ubiquitous tripeptide found in all eukaryotic cells, including all mammalian tissue. GSH is available to the mammalian organism through cellular synthesis from constituent amino acids, and also through dietary intake. Depletion of GSH in the substantia nigra is one of the earliest reported biochemical events to occur in Parkinson's disease (PD). 1 e GSH content of the substantia nigra in PD has been shown to be approximately 40% lower than controls 2,3 and the degree of disease severity is correlated with the extent of GSH loss. 4 Evidence of glutathione depletion is also evident in related disorders of the nigrostriatal system, such as progressive supranuclear palsy and multiple system atrophy. 5 Post-mortem studies document glutathione deciency in PD patients, and recently glutathione deciency has been demonstrated in the cerebrospinal uid of Lewy body disease patients. 6 Pathological hallmarks of neurode-generative diseases include mitochondrial dysfunction, oxidative stress, neuroinam-mation, and apoptosis. No medications are available to interfere with this degenerative process; rather, PD therapeutic strategies are targeted solely at dopamine replacement and symptom management. Even with medica-Abstract Reduced glutathione (GSH), an abundant essential antioxidant capable of scavenging reactive oxygen species and reactive nitrogen species in both cytosol and mitochondria, is one of the primary antioxidant defence systems of the central nervous system. Among its many roles, GSH is a substrate for glutathione peroxidase, where it inactivates hydrogen peroxide, a mediator of neurode-generation. GSH holds potential as a neuroprotective strategy capable of reducing radicals, preventing mitochondrial dysfunction, and subsequent cell death. Whereas humans are typically capable of supplying GSH in quantities sucient for function, the production of GSH appears inadequate in some circumstances. Preliminary data now exists to warrant consideration of supplemental GSH as a conditionally essential nutrient in individuals with evidence of nigrostriatal degeneration, such as in Parkinson's disease. While there are several potential methods for administering supplemental (i.e., exogenous) GSH, intranasal administration might be the preferable method when attempting to augment GSH levels within the central nervous system and to slow neurodegeneration among patients having Parkinson's disease. A safety survey and Phase I study of intranasal glutathione are currently underway to evaluate the safety and tolerability of this novel method of administration.