Rewriting the Choesterol Code

Article by Dr. Donald Greig

Most of us are familiar with the idea of taking a daily tablet to lower cholesterol. For many patients, that tablet is a statin, and statins have been one of the great success stories of modern preventive medicine.

But a recent article described something quite different: the possibility that, one day, a single injection could produce long-lasting - perhaps even lifelong - reductions in “bad” cholesterol.

The research is still early, and it is important not to overstate it. These treatments are not yet routine clinical care. They are being tested in small groups of patients and will need longer follow-up to confirm safety and durability. But the idea is remarkable: rather than taking a medicine every day to influence cholesterol production, gene-editing treatments may be able to alter the biological instructions that control how much cholesterol and other blood fats circulate in the body.

Why Cholesterol Matters

Cholesterol is a fatty substance that the body needs to build cell membranes, produce hormones and support normal function. The problem is not cholesterol itself, but the wrong amount in the wrong place.

The cholesterol we worry most about is low-density lipoprotein cholesterol, or LDL cholesterol. This is often called “bad cholesterol” because high levels contribute to the build-up of fatty deposits inside the arteries.

Over time, these deposits can form plaques. Plaques can narrow the arteries, reduce blood flow and, if they rupture, trigger a blood clot. This is one of the major mechanisms behind heart attacks and strokes.

Another type of blood fat, triglycerides, can also contribute to cardiovascular risk, particularly when they are raised alongside other metabolic risk factors such as diabetes, obesity or fatty liver disease.

So the goal of cholesterol treatment is not cosmetic. It is not simply about improving a number on a blood test. It is about reducing the lifetime risk of heart attack, stroke and premature cardiovascular disease.

Statins: The Current Foundation of Cholesterol Treatment

For decades, statins have been the cornerstone of cholesterol treatment.

Statins work by blocking an enzyme in the liver called HMG-CoA reductase. This enzyme plays a key role in the liver’s production of cholesterol.

When a statin reduces cholesterol production inside the liver, the liver responds by increasing the number of LDL receptors on its surface. These receptors act like catchers’ mitts, pulling LDL cholesterol out of the bloodstream. The result is a lower level of LDL cholesterol circulating in the blood.

This is why statins are so useful: they do not merely change a laboratory value; they reduce cardiovascular events. Large studies over many years have shown that lowering LDL cholesterol with statins reduces the risk of heart attacks, strokes and death from vascular disease.

Statins are also practical. They are taken by mouth, are inexpensive, widely available, and have been studied in millions of people.

For many patients, they remain the best first-line option.

Why Some Patients Need More Than a Statin

Although statins are highly effective, they are not perfect for everyone.

Some patients have very high cholesterol because of inherited conditions such as familial hypercholesterolaemia, often shortened to FH. People with FH are born with impaired cholesterol-clearing machinery, which means LDL cholesterol can be very high from a young age. Without treatment, their lifetime risk of early heart disease is substantially increased.

Other patients cannot tolerate higher doses of statins, or they may still have cholesterol levels above target despite taking statins regularly. Some people also struggle with taking daily medication consistently over many years, especially when the treatment is preventive and they feel well.

For these reasons, cholesterol treatment has already expanded beyond statins.

There are now other options, including ezetimibe, which reduces cholesterol absorption from the gut; PCSK9 inhibitors, which help the liver remove more LDL cholesterol from the blood; and inclisiran, a twice-yearly injection that uses small interfering RNA to reduce PCSK9 production.

The new gene-editing approaches described in the article go a step further again.

What the New Gene-Editing Treatments Are Trying to Do

The article described two early clinical trials using gene-editing technology to lower cholesterol.

One trial, led by researchers in the United States and involving sites including Australia, New Zealand and Britain, tested a treatment called CTX310. This uses tiny particles to carry a CRISPR gene-editing tool into liver cells.

Its target is a gene called ANGPTL3.

ANGPTL3 helps regulate blood fats, including LDL cholesterol and triglycerides. Some people are naturally born with mutations that reduce or disable ANGPTL3 activity. These individuals tend to have very low levels of cholesterol and triglycerides and appear to have a lower risk of heart disease.

CTX310 is designed to imitate that protective genetic pattern. In the highest-dose group, the article reported substantial reductions in ANGPTL3, LDL cholesterol and triglycerides after a single intravenous infusion.

The second trial, from researchers in China, focused on patients with familial hypercholesterolaemia and targeted a different gene: PCSK9.

PCSK9 normally reduces the liver’s ability to clear LDL cholesterol. It does this by breaking down LDL receptors. If PCSK9 is very active, fewer LDL receptors are available, and LDL cholesterol remains higher in the bloodstream.

By switching off PCSK9, the liver can keep more LDL receptors and remove more LDL cholesterol from the blood. This is the same broad pathway already targeted by existing PCSK9-lowering medicines — but gene editing aims to produce a longer-lasting effect after a single treatment.

How This Differs From Statins

The difference between statins and gene editing is not simply that one is a tablet and the other is an injection. They work at a different level.

A statin works like a daily instruction to the liver: make less cholesterol and remove more LDL from the blood.

Gene editing aims to make a more permanent change to the underlying biological machinery. It attempts to alter or switch off a gene involved in cholesterol regulation so that the body continues producing a cholesterol-lowering effect over time.

A useful comparison is this:

• Statins are like adjusting the thermostat every day.

• PCSK9 injections or inclisiran are like setting a longer timer.

• Gene editing is more like rewiring part of the control system.

That is why the idea is so exciting — but also why it requires careful caution. A long-lasting effect can be a major advantage if the treatment is safe and effective. But if a treatment is designed to last for years, or possibly for life, we need to be very confident about its long-term safety.

Why This Could Be a Better Option for Some Patients

If gene-editing treatments prove safe and effective in larger and longer studies, they could offer several advantages.

First, they may help patients with very high genetic cholesterol levels who need substantial LDL reduction from early adulthood or even childhood.

Second, they may reduce the burden of taking lifelong medication. Many cardiovascular treatments work only if taken consistently. In real life, adherence is difficult. People forget tablets, stop medication when they feel well, or struggle with side-effects or cost. A single treatment that provides durable cholesterol reduction could remove some of that burden.

Third, they may help patients who cannot reach cholesterol targets despite existing therapy.

Fourth, they may reduce both LDL cholesterol and triglycerides, depending on the gene targeted. This could be particularly useful in selected patients with complex lipid disorders.

However, “better” does not mean better for everyone.

For most patients today, statins remain safe, proven, accessible and effective. Gene editing is more likely, at least initially, to be considered for people at particularly high risk - for example, those with familial hypercholesterolaemia or those who cannot achieve adequate cholesterol control with current treatments.

The Safety Question

The article rightly notes that these trials are still under long-term observation.

This is essential.

Gene-editing therapies must be assessed not only for whether they lower cholesterol, but also for whether they do so safely over many years. Researchers need to look for unintended edits, liver inflammation, immune reactions, unexpected metabolic effects and whether the cholesterol reduction remains stable.

It is also important to remember that early trials are usually small. Dramatic results in a small number of volunteers are encouraging, but they are not the same as the evidence we have for statins, which have been studied across very large populations for decades.

This does not make the new research less exciting. It simply means we should place it in the right category: promising, potentially transformative, but not yet established routine care.

What Patients Should Take From This

For patients, the message is one of cautious optimism.

We may be entering an era in which some forms of cardiovascular risk can be treated at their genetic source. That is a major shift in thinking.

But for now, the basics still matter enormously.

The proven ways to reduce cardiovascular risk remain:

• knowing your blood pressure;

• checking your cholesterol;

• not smoking;

• treating diabetes well;

• maintaining regular physical activity;

• eating a heart-healthy diet;

• managing weight;

• sleeping well;

• limiting excess alcohol;

• and taking prescribed medication consistently.

For patients already taking statins, this news should not be a reason to stop them. Statins remain one of the most evidence-based tools we have for preventing heart attacks and strokes.

Instead, this research should be seen as a glimpse of what may come next: a future in which treatment can be more durable, more personalised and perhaps less dependent on daily medication.

A New Chapter in Prevention

Heart disease remains one of the leading causes of illness and death worldwide. Much of it develops silently over many years, long before symptoms appear.

That is why prevention is so powerful.

The possibility of a one-off gene-editing treatment for cholesterol is exciting because it targets prevention at a very deep biological level. It asks whether we can reduce risk not just by managing cholesterol day to day, but by altering the genes that control cholesterol itself.

That is a profound idea.

But it is also one that needs humility. In medicine, breakthroughs only become truly valuable when they are proven to be safe, effective, affordable and accessible.

For now, statins remain the foundation. Newer injections already offer additional options for some patients. Gene editing may represent the next frontier.

If the promise holds, the future of cholesterol treatment may look very different: fewer daily tablets for some, more precise treatment for those at highest risk, and a stronger focus on preventing heart disease before it has the chance to strike.

If you are concerned about your risk of heart disease and high cholesterol, make an appointment to discuss with Dr. Greig

Disclaimer: This newsletter is for informational purposes only and does not constitute medical advice. Always consult your healthcare provider for any medical concerns.