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Researchers helping to tackle one of the biggest killers in young athletes
At 5.43pm on 12 June 2021 the sporting world was shocked when Danish footballer Christian Eriksen suffered a cardiac arrest while playing Finland in the European Championships. He was technically dead for ‘three to four minutes’ before CPR revived him.
The most common cause of cardiac arrest in young athletes is Hypertrophic Cardiomyopathy (HCM) –a disease in which the heart muscle becomes thickened (hypertrophied). The thickened heart muscle becomes damaged over time, which in the rare cases leads to cardiac arrest, as may have happened with Christian Eriksen, but certainly underlined the death of Man City’s Marc Vivien Foe and collapse of the former Bolton player Fabrice Muamba.
Understanding HCM – including possible drug treatments – is vital in saving lives. In a big step forward, a team from Kent has become the first lab in the UK to directly image how muscle activity is controlled at a microscopic level.
This technique was used to show that the recently FDA-approved drug, Camzyos™ (mavacamten) only partially reduces the activity of skeletal muscle by “putting to sleep” the motor proteins that generate contraction. This means it is more targeted to cardiac muscle, where it more strongly reduces muscle activity, which is thought to be the causative mechanism of HCM.
Professor Neil Kad, who led the research from Kent’s School of Biosciences, said: ‘It is vitally important to understand the mechanism of disease and also the mechanism of drug action, which is not always fully understood. In this case, we also found there was an additional reserve of motors incapable of being shut down by this drug, we don’t know why, but it is important that we find out.
‘Our next steps include working with scientists in Italy and the USA to study stem cell derived cardiac cells containing disease-causing mutations. Ultimately, we need to understand how each mutation results in disease and how drugs can offset these effects, paving the way for personalized medicine. This new technology offers a new way to understand muscle contraction, and also offers a new hope for the development of drugs against a very cruel disease.
‘With support we will be able to understand how mutations result in disease, paving the way to developing a drug screening technology. Our goal is to have a pill tailored to the type of mutation so that people with this disease can lead normal lives and play sport.’
You can view a short video of Professor Kadd explaining his research on our YouTube channel: Researching Hypertrophic Cardiomyopathy (HCM) | Professor Neil Kad | University of Kent – YouTube
The research paper titled ‘Single molecule imaging reveals how mavacamten and PKA modulate ATP turnover in skeletal muscle myofibrils’ is published by the Journal of General Physiology. Doi: 10.1085/jgp.202213087.