Pharmacological inhibition of Hippo pathway for the treatment of adverse cardiac remodelling

Complete

04/11/2021

North West

Drug discovery/ Therapeutics

Awarded amount: £151,203

Grant scheme: TRP

Institution: University of Manchester

Principle Investigator: Prof Delvac Oceandy

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Heart failure is a major cause of disease and death, thought to affect 1 million people a year in the UK.

One of the underlying causes of heart failure is changes to the hearts structure, known as cardiac remodelling, following a major cardiac event, such as a heart attack.

This research group had previously identified a group of proteins that are part of the “Hippo” pathway that appear to play a significant role in the growth and survival of heart cells under diseased conditions. If these proteins can be regulated, it may allow heart damage to be repaired so that it cannot progress into heart failure. This project focused on a newly identified drug, MRT137, to test whether it could control these proteins in laboratory models.

The overall results showed positive trends towards improved heart function and decreased adverse remodelling.

However, the impacts were small, and further work will be needed to optimise dosing and delivery systems. This study has confirmed MRT137 as a target drug for heart repair and the group is now commencing a follow a study to confirm and expand the findings of this study.

A manuscript is in preparation for publication in late 2024, with plans to present the findings at a major international conference in 2025.