Wallace Bridge, PhD

Associate Professor Wallace Bridge (BSc, MAppSc, PhD) has 39 years academic and industrial research experience in Australia and overseas and currently holds an Honorary academic position in the School of Biotechnology and Biomolecular Science, Faculty of Science, UNSW Sydney, Australia where he has been a member of Faculty for 25 years. Since 1999, Wallace has been actively involved in research aimed at investigating the potential for the glutathione precursor, gamma glutamylcysteine (GGC) to offer a solution to cellular glutathione depletion/oxidative stress related medical conditions.

Glutathione is ubiquitous in nature and is produced by all cells of organisms, from bacteria, plants to animals, that utilize oxidative phosphorylation to derive metabolic energy. Acute or chronic cellular glutathione depletion and consequent oxidative stress is associated with most medical conditions. Glutathione synthesis involves two ATP dependent enzyme catalysed reactions. The first reaction joins glutamate and cysteine to form GGC, and the second adds a glycine to form the tripeptide, glutathione. Cellular glutathione homeostasis involves glutathione interacting with the enzyme that forms GGC (glutamate cysteine ligase, GCL) to effectively stop GGC and consequently glutathione production. Different types of cells have different homeostatic setpoints, for the liver it is ~ 10 mM and for neurons it is ~1 mM. The risk of cellular oxidative stress occurs when the environment of the cells and associated tissue becomes exposed to increased levels of free radicals that overwhelm the cells normal homeostatic level of glutathione production, or when the cell’s homeostatic regulatory control becomes dysfunctional, and they still make GGC and glutathione but not at sufficient levels to avoid oxidative stress.

Since GGC is the product of the regulatory control enzyme it offers an opportunity as a supplement to boost cellular glutathione levels above homeostasis, which could address any oxidative stress. As such, GGC has a theoretical metabolic advantage over N-acetylcysteine (NAC) and glutathione supplements, which cannot bypass this homeostatic control. This disadvantage of NAC and glutathione may explain why they repeatedly fail to demonstrate significant therapeutic benefits in clinical trials. Published UNSW sponsored human clinical studies have demonstrated GGC’s unique bioavailability to increase cellular glutathione levels above homeostasis. Wallace is collaborating with numerous UNSW and external researchers to investigate GGC’s therapeutic potential in a range of medical conditions, including cystic fibrosis and Alzheimer’s disease. Other independent researchers are also beginning to publish reports supporting GGC’s efficacy in various health models. During Wallace’s presentation he will describe the biochemistry of glutathione synthesis and GGC’s unique advantage for potential therapeutic applications. He will give an overview of recent findings in studies investigating GGC in various disease models, with a focus on neurodegenerative disorders.