Friday 16 September 2011
Update on our cutting edge FSH research
The research team and two members of our Lay Panel recently visited Dr Peter Zammit's laboratory for an update on their research into facioscapulohumeral muscular dystrophy (FSH). We were also lucky to hear from a collaborator who was visiting the lab from Belgium. Trevor Thomas from the Lay Panel tells us about the visit.
Recently, Stuart Watt and myself from the Lay Panel accompanied the Muscular Dystrophy Campaign research team on a visit to King's College to meet Dr. Peter Zammit and his team who are carrying out research on FSH. The enthusiasm and commitment of the team shone out from their slide presentations and from the explanations given during our tour of the laboratory. It really was an uplifting experience.
Dr Zammit gave us an introduction to how muscle grows and maintains itself, including the role of the muscle stem cells (satellite cells). The satellite cells lie dormant within the muscle and then "switch on", multiply, and turn into new muscle cells as necessary for growth or repairs.
He then outlined current knowledge of the DNA abnormality which is the underlying cause of most cases of FSH. It is now thought that the DNA defect results in a toxic protein called DUX4 being produced in a proportion of the muscle cells, which is likely to kill them. The defect also interferes with the ability of the satellite cells to repair the muscle. However, in both cases the chain of events inside the cells is far from being fully understood. Better understanding is essential for devising effective treatments. This is the area of research of Dr. Zammit's group.
Contents:
- How are stem cells involved in FSH?
- Why do muscle cells die in FSH?
- Working towards potential therapies
- Further information and links
How are stem cells involved in FSH?
Louise Moyle outlined the research she is doing for her PhD, funded by the Muscular Dystrophy Campaign in partnership with Kings College London. She is investigating how the DNA abnormality affects the functioning of the satellite cells. She explained that the cells in our bodies are extremely complex and have to be highly regulated in order to function well. This involves the production of various proteins, the main constituent of cells. The proteins are manufactured under the control of instructions encoded in the DNA.
Some kinds of protein can influence what instructions the DNA gives for making other proteins. As a result, there are many chains of events taking place all the time, which are known as "pathways". This is how the cell normally maintains a healthy balance under all conditions. However, in FSH the DNA defect produces an abnormal protein called DUX4 which alters the instructions given by the DNA for making other proteins, and so disrupts the activities in the satellite cells and muscle fibres.
Louise is trying to find out what changes to the normal "pathways" are caused by DUX4 protein in satellite cells. Of course, the main aim is to identify changes to the "pathways" that lead to muscle weakness and poor muscle repair. She uses very advanced techniques, including the use of luminous antibodies to find and mark the different proteins. Changes in luminosity show which proteins are increased and which are reduced when DUX4 protein is added to a satellite cell. In this way it is possible to identify which "pathways" are opened or closed by the DUX 4 protein.
Why do muscle cells die in FSH?
Dr Janet Davies, another member of Dr Zammit's group, is investigating the mechanism by which DUX4 protein causes muscle cells to die. She explained that cells are programmed to die in certain situations, e.g. to prevent cancer. In FSH the DUX4 protein is known to kill muscle cells by triggering this process. The aim of Janet's research is to find out where DUX4 protein intervenes in the normally tightly regulated "pathway" that leads to "programmed cell death", as that knowledge would be a starting point for dealing with it.
Working towards potential therapies
The final slide presentation was by Dr Alexandra Tassin from Mons University in Belgium. She is from Professor Alexandra Belayew's research group. They were the first to detect the "rogue" protein DUX4 and show that it results from the unusual DNA defect of FSH. It took them several years of difficult work to find the DUX4 protein, even though its existence was already suspected after the "recipe" for it had been found inside the abnormal part of the DNA.
We were amazed at what we learned from Dr Tassin. Recent research has shown how FSH muscle cells can be prevented from making DUX4 protein by treating them with a small piece of DNA or "antisense oligonucleotide". This is similar to the "molecular patch" currently being used in clinical trials for Duchenne muscular dystrophy. So far the experiments have been limited to muscle cells grown in the laboratory. Alexandra is now spending a few months at King's College in a collaborative effort to develop a mouse model to test a potential therapy. Watch this space!
The visit to King's College gave us an inkling of the complexity of the problem being tackled, and also the high level of technology and expertise being applied. Dr Peter Zammit and his team are very impressive in their commitment and professionalism and they certainly seem to be getting to grips with FSH. The work seems to be in very good hands.
Further information and links
More information about FSH.
More FHS research news.
Read about the research we fund into FSH.
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