Home » Cardiology » How breakthrough gene-editing medicines could lower cholesterol — permanently

Dr Sekar Kathiresan

Cofounder and Chief Executive Officer, Verve Therapeutics

Dr Andrew Bellinger

Chief Scientific Officer and Chief Medical Officer, Verve Therapeutics

Gene-editing medicines that permanently and significantly lower cholesterol and the risk of heart attacks could revolutionise the field of cardiovascular disease. 

Finding a way to prevent and treat heart attacks is a personal quest for Dr Sekar Kathiresan, Cofounder and Chief Executive Officer of genetics medicines company, Verve Therapeutics

“Like so many families, ours has lost loved ones to cardiovascular disease,” he says. “My grandmother, uncle and brother all died of premature heart attacks. Both my uncle and brother were only 42 years old when they passed. My family’s experience led me to these questions: Why do some people have heart attacks at a young age — and might some be naturally protected?” 

Dr Kathiresan found the answers when he and other human genetics researchers discovered people who naturally lacked any of several cholesterol-raising genes including PCSK9 and ANGPTL3. This meant they had a disease-causing gene permanently switched off, leading to very low levels of low-density lipoprotein cholesterol (LDL-C, so-called ‘bad cholesterol’) in their blood and, as such, were naturally protected from the risk of heart attacks. “Whereas, people with high levels of LDL-C are more likely to suffer a heart attack,” explains Dr Kathiresan. 

The ability to permanently switch off a disease-causing gene 

This discovery led to Verve’s mission to develop a pioneering medicine: one that mimics natural protection by turning off the PCSK9 gene in high-risk people, thereby with the potential to powerfully lower their LDL-C levels. “To do this, we chose a second generation gene-editing technology called base editing,” explains Dr Andrew Bellinger, Chief Scientific Officer and Chief Medical Officer at Verve Therapeutics. “First generation gene-editing technology cuts the DNA in the gene in a specific location. However, base editing is an even more targeted approach which provides us with the potential to permanently change a disease-causing gene. Rather than cutting it, it’s more like correcting a spelling error with a pencil eraser.” 

This new approach — called VERVE-101, which is now at the clinical trial stage — is delivered as a one-time intravenous medication. 

It could be good news for people struggling to control high cholesterol with daily pills or intermittent injections. “Despite the medicines we have available to treat cholesterol, only about half the patients who have suffered a heart attack are currently taking an LDL-C lowering medicine,” says Dr Bellinger. “The chronic care model requires daily pills or intermittent injections over decades and places a tremendous burden on patients, providers, and the healthcare system, leading to a large unmet need. We hope to offer patients a new option – a one-time treatment, permanent lowering of LDL-C.” 

We’re extremely grateful to the participants
in our study for trusting us and furthering
our understanding of HeFH.

Dr Andrew Bellinger

Innovation passport to speed drug development 

The company hopes that it will be able to use VERVE-101 to dramatically alter treatment for heterozygous familial hypercholesterolemia (HeFH), an inherited genetic disorder that causes high cholesterol, and ultimately, ASCVD. Nevertheless, Dr Bellinger admits there’s still a long road ahead before this medication becomes available to patients on the NHS. 

“We’re extremely grateful to the participants in our study for trusting us and furthering our understanding of HeFH,” he says. “At present, we’re running a clinical trial in New Zealand and the UK, with regulatory clearance from the MRHA (Medicines and Healthcare products Regulatory Agency), the UK regulatory authority. 

“We’ve also received an innovation passport from MRHA and NICE (National Institute for Health and Care Excellence) that is designed to accelerate drug development and access in the UK to novel therapies. We’re hopeful that it will help speed up the process so that we can make it available to everyone who needs it.” 

A future with less risk of heart attacks 

 Ultimately, Dr Kathiresan and Dr Bellinger believe that the therapy will be a medical game-changer. “It won’t just revolutionise the way we lower cholesterol,” says Dr Bellinger. 

“It could revolutionise the whole field of cardiology and cardiovascular disease. This is how we will treat heart disease in the future. We won’t wait for someone to have a heart attack, give them a stent and put them on five different medicines. Instead, we will be lowering their risk of heart attacks earlier by lowering their LDL-C with one-time therapies. That’s a really exciting thought.”

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