Funding award to accelerate TB research
Published on 25 September 2023
Mouse models with a human drug metabolism have the potential to transform preclinical research, say University of Dundee experts.
Researchers at the University’s Schools of Life Sciences and Medicine have received almost $1 million from the Bill & Melinda Gates Foundation with the aim of accelerating the development of new drugs in the treatment of tuberculosis (TB).
The University of Dundee Drug Discovery Unit (DDU) has previously received support from the Gates Foundation to discover and develop new treatments for TB. The current funding has been awarded to evaluate and exploit a unique mouse model, 8HUM, which metabolises drugs like humans. 8HUM was originally developed by Professor Roland Wolf in a collaboration between CXR Biosciences and Taconic Farms in a project funded by Scottish Enterprise and subsequently in the University together with Professor Colin Henderson.
“The 8HUM mouse has potential to be a game changer in early drug discovery and development” said Professor Kevin Read, from the DDU and lead investigator on this project.
“We have shown this model to closely replicate the human metabolic process which control the way drugs are metabolised and eliminated in patients. We have spent the last 18 months extensively validating its ability to address a number of common drug discovery and development challenges.
“One such challenge is bypassing mouse specific metabolism issues in order to demonstrate efficacy in a mouse model of disease, a key stage gate for compound progression in a drug discovery and development programme.
“Much time and resource is often lost in early drug discovery fixing a mouse specific problem rather than retaining focus on optimising a compound for human use. This is resolved using the 8HUM model.
“Being able to apply the 8HUM in TB drug discovery and development will really help to expedite much needed new treatments for this disease”.
Tuberculosis remains a leading cause of death worldwide, with an estimated 10.6 million new cases and 1.6 million deaths in 2021. There is an urgent need to develop new drugs to combat the illness, with drug-resistant strains having emerged.
Mice are used for research purposes in Dundee under Home Office licence authority, and after ethical review, and only when no alternatives exist.
Professor Wolf said, “These humanised models have the potential to transform the drug development process by reducing development times and increasing the probability that drugs will be used efficaciously and safely in the clinic. They could replace conventional mice in drug development and reduce animal usage”.
“When patients are taking a combination of drugs, which at the present time can be many, there is the potential for one drug to compromise the efficacy of others. Indeed, such interactions can cause serious, life threatening drug side effects.
“The humanised models have the potential to predict such adverse drug/drug interactions prior to the drugs entering the clinic. This of particular importance in areas of the world where TB is prevalent because of the concomitant treatment of other diseases such as HIV or malaria.”
Dr Paul Rounding CEO of PhaSER Biomedical, added, “We are delighted the Bill & Melinda Gates foundation are supporting research to exploit the 8HUM mouse model for the accelerated development and use of drugs in the treatment of disease where there continues to be an unmet clinical need”
“The 8HUM model is also now being further exploited by PhaSER Biomedical Ltd in other collaborations involving the University of Dundee and others”.
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