Translational Research Project Grant
Dr T Scott Bowen, University of Leeds
Summary: Many patients with heart failure have severe muscle weakness but no effective drug treatments are available. This project will investigate the causes of muscle weakness in heart failure and aims to identify new drug treatments for loss of muscle strength to improve symptoms, quality of life and survival in heart failure patients.
Muscle wasting and weakness is common in many illnesses. This is found in both the breathing and leg muscles, which causes breathlessness and disability. Loss of muscle strength affects simple daily activities such as doing housework, showering, and gardening. Importantly, muscle weakness is a very strong predictor of poor quality of life and early death in patients with heart failure. Around 1 million people in the UK have heart failure and numbers are increasing. Many patients with heart failure have severe muscle weakness but no effective drug treatments are available. It is important that we understand what causes these muscle changes so that new treatments can be developed to improve muscle strength in patients with heart failure.
Dr Bowen’s team has found that heart failure patients have higher muscle levels of a protein called ‘MuRF1’ which may have a very important role in muscle weakness caused by heart failure. When MuRF1 levels are reduced, for example by exercise training, muscle strength and mass improve in heart failure. Many heart failure patients are too ill to perform exercise training, so the team has started a new research programme to identify drugs that can block MuRF1. They have identified one novel drug that can block MuRF1 and exciting early findings show this improves muscle strength.
The main aim of this project is to provide evidence that high levels of MuRF1 in patients with heart failure causes muscle weakness and tiredness. In the lab, they will investigate in detail the role of MuRF1 and the effects of drugs that block MuRF1. In the second part of the project, they will study the changes occurring in muscles of patients with heart failure using muscle biopsies, and compare with the findings made in the lab.
If successful, this project will help us understand what causes muscle weakness in heart failure and identify new drug treatments for loss of muscle strength. Although this project will focus on heart failure, the muscle changes and involvement of the MuRF1 protein are likely to be similar in other conditions such as cancer, sepsis, lung disease, and ageing. Drug treatments which improve muscle mass and strength have the potential to improve symptoms, quality of life and survival in patients with heart failure and other conditions, and may also lead to socio-economic benefits.