LightOx Photochemistry and Photophysics
Lead Research Organisation:
University College London
Department Name: Chemistry
Abstract
LightOx, an SME based in Newcastle upon Tyne, are developing LXD191, a novel light-activated therapy targeted as a preventative treatment to eliminate early-stage/precancerous lesions that arise in the mouth before they can develop into challenging cancerous tumours. LXD191 is a molecule that, when activated by light from an LED device, elicits the generation of radical oxygen species (ROS) that are highly toxic towards precancerous cells and tissues. This kind of behaviour is common in molecules known as photosensitisers, typically utilised for a type of light-activated treatment known as photodynamic therapy (PDT). However, LightOx believe LXD191 operates through a novel mechanism that is distinct from common photosensitisers and has not been reported in the literature before. Learning more about the unique activity of LXD191 will help LightOx progress this new molecule into clinical trials and to develop innovative light-activated products for other challenging diseases.
To help them understand this fascinating new drug molecule, LightOx have formed an exciting partnership with leaders in spectroscopy and photochemistry at University College London (UCL) and the Science and Technology Facilities Council's Central Laser Facility (CLF) to develop a project that aims to fully understand the unique behaviour of LXD191, and to help LightOx bring this innovative therapy to clinical utility. The project team, comprising Dr. David Chisholm of LightOx, Prof. Helen Fielding of UCL, and Dr. Igor Sazanovich, Dr. Partha Malakar and Dr. Sneha Banerjee of the CLF are aiming to utilise the world-leading facilities at UCL and the CLF to investigate LXD191 using two cutting-edge techniques: time-resolved infrared spectroscopy (TRIR) and transient absorption spectroscopy (TA). Both techniques examine the changes that occur to LXD191 at the precise moment it is activated by light and how the molecule utilises energy from the light. TRIR measures changes in precise vibrations that occur within the bonds of LXD191's chemical structure, while TA measures the energy that this structure absorbs. These data can help build a computational model to describe how LXD191 interacts with light that the team can use to understand how this molecule destroys precancerous and cancerous cells.
There are around ~8800 cases of oral cancer diagnosed in the UK each year, with most presenting at an advanced stage with poor prognosis. The incidence has been increasing for decades, particularly in those over the age of 50, and mortality rates are not improving. Around 50% of patients die within 5-years of diagnosis, whilst a reliance on invasive surgery (used in 95% of cases) means that survivors are left with severe life-long impacts affecting swallowing, eating and speech. Prevention strategies are urgently needed to address this increasing burden of disease. LXD191 promises to be the first preventative treatment for early-stage/precancerous lesions that progress to oral cancer and this project is aimed at characterising the novel activity of LXD191 to help accelerate its development towards clinical trials, and advance the understanding of light-activated chemical processes.
To help them understand this fascinating new drug molecule, LightOx have formed an exciting partnership with leaders in spectroscopy and photochemistry at University College London (UCL) and the Science and Technology Facilities Council's Central Laser Facility (CLF) to develop a project that aims to fully understand the unique behaviour of LXD191, and to help LightOx bring this innovative therapy to clinical utility. The project team, comprising Dr. David Chisholm of LightOx, Prof. Helen Fielding of UCL, and Dr. Igor Sazanovich, Dr. Partha Malakar and Dr. Sneha Banerjee of the CLF are aiming to utilise the world-leading facilities at UCL and the CLF to investigate LXD191 using two cutting-edge techniques: time-resolved infrared spectroscopy (TRIR) and transient absorption spectroscopy (TA). Both techniques examine the changes that occur to LXD191 at the precise moment it is activated by light and how the molecule utilises energy from the light. TRIR measures changes in precise vibrations that occur within the bonds of LXD191's chemical structure, while TA measures the energy that this structure absorbs. These data can help build a computational model to describe how LXD191 interacts with light that the team can use to understand how this molecule destroys precancerous and cancerous cells.
There are around ~8800 cases of oral cancer diagnosed in the UK each year, with most presenting at an advanced stage with poor prognosis. The incidence has been increasing for decades, particularly in those over the age of 50, and mortality rates are not improving. Around 50% of patients die within 5-years of diagnosis, whilst a reliance on invasive surgery (used in 95% of cases) means that survivors are left with severe life-long impacts affecting swallowing, eating and speech. Prevention strategies are urgently needed to address this increasing burden of disease. LXD191 promises to be the first preventative treatment for early-stage/precancerous lesions that progress to oral cancer and this project is aimed at characterising the novel activity of LXD191 to help accelerate its development towards clinical trials, and advance the understanding of light-activated chemical processes.
