Gene-ius: repairing the gene for a dangerous heart condition

Today marks a milestone in gene editing as after years of trying, scientists have successfully removed a dangerous faulty gene from human embryos. The gene at the centre of the study is responsible for hypertrophic cardiomyopathy (HCM), a heart condition which is passed down in genes and can lead to sudden death if it is not diagnosed.

The condition at the centre of the story

Every week in the UK 12 people aged 35 and under die of an undiagnosed heart condition. HCM is the biggest cause of these deaths and around 120,000 people are living with the condition across the country. In people with HCM the muscular wall of the heart — the myocardium — becomes thickened, making the heart muscle stiff. This thickening makes it harder for the heart to pump blood out of the heart and around your body and can cause potentially fatal abnormal heart rhythms.

A revolution in diagnosis and treatment

Research in to the genes responsible has revolutionised diagnosis and treatment of HCM over the past four decades. In the 1980s BHF funded researchers Bill McKenna and Hugh Watkins started searching for the possible genetic causes of HCM. After a decade of painstaking research McKenna and Watkins were among the first to find faulty genes underlying the condition and have since discovered more.

Professor Hugh Watkins in his lab in Oxford.

As a BHF Professor, Hugh Watkins used these findings to set up the first genetic testing service for HCM in the UK. This meant for the first time, parents, siblings and children of someone known to have a disease-causing mutation could find out if they also had it, and get help to prevent a crisis. The initial trial found nearly 700 people with faulty genes and the test was so cost-effective it was approved as an NHS service. Through the Miles Frost Fund we’re now trying to make this testing available nationwide.

But, despite this progress, there is no way to prevent or cure the condition.

‘Cutting out’ genes and ‘editing’ DNA

Gene editing throws up a new and exciting possibility — could we repair a gene in our DNA before it can cause disease?

Although gene editing is still very much in its infancy, this study provides new and exciting insight into a technique which could one day help people with inherited disorders.

The gene cutting technique involved is known as CRISPR and is being used experimentally in hundreds of labs around the world to explore the effects of very specific gene editing on cell function. In the new study, researchers used the technique to try to repair a faulty gene in sperm. Sperm from a patient carrying the HCM mutation were allowed to fertilise a human egg in the lab. They then injected a gene-editing tool called CRISPR-Cas9, which works a bit like scissors to cut out the faulty gene. The CRISPR-Cas9 tool cuts the defective DNA out of the embryo genes, and the gap in the DNA is then repaired.

The experiments showed that the technique could produce 4–8 cell embryos in which the gene had been repaired in every cell. At this point, the experiments were terminated — though the conclusion is that if allowed to grow further and be implanted the embryo would give rise to a child in which the faulty HCM gene was no longer present.

With revolution comes controversy

CRISPR is a revolutionary leap in science, but for many it comes with controversy and concern. The ability to repair faulty DNA in embryos has brought the topic of ‘designer babies’ to the table. If we can edit out faulty genes, can we edit how our children will look? In the future, people believe scientists may be able to edit embryonic genes during IVF to not only eliminate the genes that cause disease, but pre-determine whether the child will have green eyes, brown hair, and so on. These are possibilities that most would regard as unethical: curing a potentially fatal condition is very different from re-designing healthy babies.

Some scientists have concerns over the safety of CRISPR, in particular the precision of CRISPR-Cas9 in finding its faulty DNA target. Questions are also being raised over who should decide how CRISPR is used, and how it should be regulated. These questions must be answered before gene editing will stand a chance of eradicating inherited diseases.

A scan of someone with an implantable cardioverter defibrillator (ICD) fitted. Sometimes people with HCM will have an ICD fitted to shock their heart if it enters a dangerous abnormal heart rhythm, and prevent a cardiac arrest.

Wiping out conditions like HCM

Today’s breakthrough is significant. It brings us a step closer to treatments that could stop deadly conditions like HCM being passed down through generations. This could be transformative for families today at risk of losing a loved one to a sudden cardiac arrest. But for each genetic mutation we might one day be able to correct, new mutations continue to occur. This is nature, and the race to fix mutations as quickly as they occur is a race we are destined to lose.

This research also highlights the importance of more research to transform this promise in to feasible treatments as quickly as possible. And all of this work needs to happen while giving careful consideration to the line between providing life-saving care and unnaturally intervening in nature.

If you enjoyed this blog you might also like:

By Rachel Sacks and Christie Norris