Reactive Oxygen Species-Activated Drugs for Tissue-Targeted Treatment of Pain

Abstract:

The delivery or activation of a drug molecule only at the site of disease is the pinnacle of medicinal chemistry. Such drugs are less likely to cause adverse effects and can result in greater efficacy compared to the active drug given systemically. Reactive oxygen species (ROS) are overproduced at localised sites in ailments collectively known as diseases of oxidative stress, of which chronic neuropathic pain is one of the most common. Current treatments for neuropathic pain include opioids, anti-depressants and anti-convulsants, all of which lack efficacy, have serious side effects and have addiction or withdrawal risks. Application of our ROS-activated technology to a drug which activates Nrf2, a transcription factor for the major anti-oxidant pathway in cells, has resulted in a potential treatment for neuropathic pain with demonstrated efficacy, tissue-targeting, and promising side-effect profile in mouse models of multiple neuropathic pain disorders.

Bio:

Dion Turner is a final year chemistry PhD student working under the supervision of Prof. Andrew Abell and Dr. Thomas Avery. He obtained a B.Sc. (Adv.) from The University of Adelaide in 2017 and subsequently completed an M.Phil. in 2020. Dion was awarded a Dean's Commendation for Master by Research Thesis Excellence for his thesis titled “Probing a Promiscuous Binding Pocket of the Proteasome”. During his PhD, Dion has been working on drug candidates which are activated via chemical reaction with reactive oxygen species, thereby localising the effect of the drug to sites of oxidative stress. This work spurred an interest in research translation and commercialisation, leading him to pitch his project to investor panels, VC firms and other sources of private investment.