£1.8 million award will fund research into inherited cardiac conditions

New knowledge about the genetic causes of heart diseases will be translated into improvements in diagnosis and treatment with a £1.8 million grant to Imperial from the Health Innovation Challenge Fund.

Roughly one in 100 of us are affected in some way by inherited cardiac conditions (ICCs). Innate propensities for heart malfunction can lie embedded within a person’s genetic code from birth, inherited from their parents.

Awarded jointly by the Department of Health and the Wellcome Trust, the funding supports the drive from bench to bedside. “We’ve been working in the area of human genetics and inherited cardiac conditions for some time,” says Professor Stuart Cook, whose team at the Medical Research Council Clinical Sciences Centre uses state-of-the-art sequencing technologies to investigate the genetics of ICCs.

“We’ve sequenced around 200 genes that are important for heart diseases that run in families. Through several recent publications, including one last year in the New England Journal of Medicine, we reveal the most common genetic mutations in familiar heart failure. This has established our pedigree in the area. Since genetics is so transferable to the clinic, we hope we can now apply research from the lab to clinical diagnostics.”

Professor Cook's team will work with researchers at the National Heart & Lung Institute and clinicians at Royal Brompton & Harefield NHS Foundation Trust to harness the growing power of genomic technologies. “The lab work will continue,and each month we recruit 80 healthy volunteers and 80 patients. This grant will allow us to employ a team of four people to take all of the data we have at this point and prepare it for use in a clinical diagnostics setting. From the bioinformatics to the lab set-up and tool development for reporting on variants, there is a huge amount of work to be done.”

Broadly, says Professor Cook, there are three main stages in the research progression. The first focus is in diagnostics: next-generation sequencing technologies will arm doctors and patients with detailed data about specific disease-causing mutations in the patient. The next goal on the horizon lies in prognostics: can therapies for individual patients be stratified according to their particular genetic condition? Finally, therapeutics – new ways of treating patients – will come from investigations into the molecular mechanisms at play. Using induced pluripotent stem cells derived from patients’ tissue and model systems, the researchers will unpick the cellular misbehaviour at the root of the diseases.

“Our focus is primarily on dilated cardiomyopathy and other causes of heart failure” says Professor Cook. “Although we deal with huge amounts of data, the commonality of the diseases provide a unifying end point. We’re building databases of information, and taking forward cellular studies of mutations that we’ve identified and understand.” If basic science and genetic research is to impact on everyday life, the link between laboratory and clinic must be forged; this new research direction will bridge the gap.