We are pleased to announce a new 3 year grant award of £248,940 to Prof Francesco Saverio Tedesco at University College London (UCL). This grant is being funded in partnership with Great Ormond Street Hospital (GOSH) Children’s Charity through their annual National Funding call.
What are the researchers planning to do?
The research team at UCL will make patient-specific 3D ‘mini-muscles and livers’ in the laboratory using cells called induced pluripotent stem (iPS) cells. iPS cells are made by taking cells from the body, such as skin cells, and genetically ‘reprogramming’ them so that they can be developed into any type of cell in the body. In this project, the cells will have come from patients with XLMTM, so the resulting 3D mini-muscles and livers will be human models of XLMTM.
The researchers will then test different gene therapies in the mini-muscle and liver models and measure what effect they have. For example, they will measure whether there is an increase in the muscle fibre size and/or a reduction in liver side effects.
Why is this research important?
In recent years, it has become clear that some people with X-linked myotubular myopathy (XLMTM) can have problems with their liver. Unfortunately, two clinical trials – one of which was testing XLMTM gene therapy – were stopped due to unexpected side effects in the liver, which sadly were fatal for four patients on the gene therapy trial. Pre-clinical studies testing the gene therapy in animal models of the condition had not shown such severe side effects in the liver.
To better predict potential side effects of treatments in clinical trials, we need preclinical models of XLMTM that are more like humans with the condition. This research project aims to develop human muscle and liver models of XLMTM and then test potential gene therapies in these models. This work will not only be valuable for future preclinical studies testing potential treatments but may also help to give a better understanding of how the XLMTM genetic change can affect how the liver works and responds to stress.
Francesco Saverio TEDESCO, MD PhD FHEA MRCPCH
Professor of Neuromuscular Biology and Regenerative Medicine
UCL Department of Cell and Developmental Biology
Senior Group Leader
The Francis Crick Institute.
Honorary Consultant Paediatric Neurologist
Dubowitz Neuromuscular Centre
UCL GOS Institute of Child Health & Great Ormond Street Hospital for Children, London, UK
Who is doing the research?
Prof Francesco Saverio Tedesco will be overseeing the research project. He has pioneered the development of mini-muscle models based on human stem cells and is an expert in neuromuscular conditions and muscle regeneration.
The research will mainly be carried out by Dr Valentina Maria Lionello, a postdoctoral researcher in Prof Tedesco’s lab. She received her PhD training under Dr Jocelyn Laporte at the University of Strasbourg, France, who is an expert in centronuclear myopathies including XLMTM. Dr Lionello’s PhD was partly funded by the Myotubular Trust, so we are truly delighted to be supporting her once again with this important research.
