The Biological Process Of Muscle Fibre Death
Along with MDUK and The Duchenne Research Fund, we are funding Professor Jenny Morgan of University College, London, to study 'Mechanisms of myonecrosis in duchenne muscular dystrophy: can we control the death of muscle fibres?'
The project started in 2014 and is being funded for three years.
What Is Necrosis?
Necrosis is the biological process by which muscle cells die in DMD, and it is not very well understood. This project aims to find out more about how a muscle fibre dies by necrosis and how this it can be prevented. The project will use a mouse model of DMD and human muscle cells grown in the laboratory. The aim is to discover if a newly identifed process called regulated cell death is part of the way muscle cells die in DMD and, if so, to search for ways to prevent this.
The researchers also aim to stop key molecules in the pathway which leads to cell death from working properly to investigate whether this could prolong the life and slow the decline of the muscles.
The first year report on this study says:
"Inflammation is implicated in the necrosis of dystrophic muscle fibres. We have data supporting our hypothesis that pro-inflammatory cytokines (proteins released by inflammatory cells) elicit cell death by necrosis in muscle cells in culture. We have identified a specific pathway that is implicated in this cell death mechanism. Inhibiting this pathway protects cultured muscle cells from death. We are currently generating mdx mice (a mouse model of Duchenne muscular dystrophy) that are deficient in this pathway. If, as we hypothesise, this genetically-modified mouse is at least partially protected against muscle fibres loss, the next step will be to design a pharmacological agent to inhibit this pathway in mdx mice."
What Is Happening With Clinical Trials?
The results will show whether regulated processes are a part of muscle fibre death in DMD. It will also show if stopping molecules on the pathway will help prevent this process.
This project is in the preclinial stage and will progress if the results of the investigation are positive.