Dilated cardiomyopathy (DCM), estimated to affect up to 260,000 people in the UK, is a major cause of heart failure and the leading cause of transplantation. The £2 million investment from the British Heart Foundation (BHF) will enable the multi-centre study to establish a cohort of 2,000 DCM patients, and to investigate the causes underpinning dilated cardiomyopathy.
DCM is a progressive disease and currently very poorly understood, with most causes unknown and research suggesting that 15% of patients do not survive beyond 5 years after diagnosis.
Some cases of DCM are known to be caused by mutations in a gene that produces a protein called titin. Titin is the largest protein in the human body and acts like a spring within muscle tissue, including the heart.
Due to a common mutation in the titin protein there are an estimated 650,000 people in the UK at risk of developing the condition. However, research by Cardiologist Dr James Ware, Clinical Senior Lecturer in Genomic Medicine and part of the BHF-funded study, has found that not all people who have a mutation in the titin protein develop DCM, which suggests there are both genetic and environmental triggers. Therefore, it is important to better understand the mechanisms of the disease to help identify interventions to treat DCM.
The BHF-funded study will utilise a combination of whole genome sequencing, alongside a number of cardiac imaging tools, and circulating biomarker measurements to provide new insights into the risk factors, underlying causes of DCM and potential environmental interactions.
The study is led by Professor Stuart Cook, Professor of Clinical and Molecular Cardiology at Imperial College London and Head of the Cardiovascular Magnetic Resonance Imaging and Genetics group at MRC London Institute of Medical Sciences. A review recently published in Nature Reviews Cardiology by Ware and Cook1 discussed the role of titin in dilated cardiomyopathy, following a landmark paper in the New England Journal of Medicine in 20122,which Cook contributed to. Ware and Cook are interested in further understanding the role of titin in DCM and published a paper last year in Nature Genetics3 on this research. Their involvement in this study further illustrates the positive role clinicians can play in medical research.
Professor Stuart Cook, Professor of Clinical and Molecular Cardiology at Imperial College London, is leading the study. Speaking about the complex nature of the condition, he said:
“For about 1 in 4 patients with DCM we can find a genetic cause, but that leaves us with hundreds of thousands of people with DCM that we cannot explain, which hinders our ability to diagnose and treat the patients or help their families.
“There are currently no targeted treatments that are specific for DCM, but as we get a better understanding of the genes which cause the condition, we can hope to develop new treatments which target these genes and pathways.”
Providing time and space for clinicians to develop their research skills is actively encouraged at MRC LMS through the Chain-Florey Clinical Research Scheme, now in its tenth year. The scheme offers clinicians an opportunity to carry out a PhD, pursue further research through the clinical lectureship scheme and in 2018 further progress their research through the clinical senior lectureship scheme.
The Chain-Florey scheme is supported by the Medical Research Council, NHS National Institute for Health Research and Imperial College London. It is named in celebration of one of the greatest collaborations between medicine and science: Howard Florey, a clinically trained pathologist, and Ernst Chain, a biochemist, who shared the 1945 Nobel Prize in Physiology or Medicine with Alexander Fleming for their work in discovering, developing and producing the first antibiotic: penicillin.
1 Ware JS, Cook SA, 2018, Role of titin in cardiomyopathy: from DNA variants to patient stratification, Nat Rev Cardiol, Vol:15, Pages:241-252
2 Herman, D.S., Lam, L., Taylor, M.R., Wang, L., Teekakirikul, P., Christodoulou, D., Conner, L., DePalma, S.R., McDonough, B., Sparks, E. and Teodorescu, D.L., 2012. Truncations of titin causing dilated cardiomyopathy. New England Journal of Medicine, 366(7), pp.619-628.
3 Schafer S, de Marvao A, Adami E, et al., 2016, Titin truncating variants affect heart function in disease cohorts and the general population, Nature Genetics, Vol:49, ISSN:1546-1718, Pages:46-53
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