Development of microRNA-19 as a marker, mediator and treatment for liver injury

Acute injury to the liver is a life-threatening consequence of paracetamol overdose – a clinical scenario that is extremely common (around 100,000 cases attending UK hospitals every year, cost £50million). Currently, we do not have the tools to precisely identify who must be treated and we only have one drug that provides protection only against early liver damage. No current treatment stimulates an injured liver to recover so reducing the demand for liver transplantation.

By systematically studying this poisoning in humans we have identified a microRNA (miR-19) in the blood that falls substantially with severe liver damage. Going from humans into mice and fish models we, and others, have demonstrated that only one cell type in the liver (hepatic stellate cells) makes miR-19. miR-19 falls when these cells are activated by liver injury and this fall prevents liver cell regeneration and organ recovery. Therefore, we propose that miR-19 is a marker, mediator and new treatment for liver injury.

In addition to treating paracetamol overdose, miR-19 also has great potential value to the UK pharmaceutical industry because new drugs carry a risk of liver toxicity that can result in huge financial loss. We have partnered with AstraZeneca to ensure our work has commercial value, in addition to benefiting patients.

This project will determine if miR-19 measurement in humans can help doctors identify which patients have life-threatening illness and will use world-leading disease models in the Universities of Edinburgh and Liverpool to address a series of cogent aims that define the mechanistic contribution of miR-19 to liver failure. MicroRNA therapies are now coming to patients so, finally, we will test if replacing miR-19 can help the liver to recover from damage.