End heart attacks by editing human DNA

(ORDO NEWS) — Even after decades of breakthrough drugs to prevent heart attacks, they remain the world’s leading cause of death. Commercially available pills and injections help lower cholesterol levels, which clog blood vessels and put people at risk of heart attack.

But not everyone has access to them, and some don’t want to stick to a lifelong treatment plan. Verve Therapeutics Inc. offers a radical solution: to change the human genome – the instructions for the body – and stop the accumulation of bad cholesterol.

“We are on the cusp of potentially transforming this model into a one-time treatment,” says Sekar Katiresan, chief executive officer of the Cambridge, Massachusetts-based company.

Verve plans to initially target those who have already suffered a heart attack due to extremely high cholesterol levels caused by an inherited disease known as familial hypercholesterolemia, which affects 31 million people worldwide.

If the drug can help lower low-density lipoprotein (LDL), or “bad” cholesterol, in this group, the company will look to expand its patient pool, eventually planning to give it to younger people as a preventive measure, though it’s too early to say when. it can happen.

The company is backed by Google Ventures (now known as GV) and established biotech investors Arch Venture Partners and F-Prime Capital. The company went public in June, reaching a market capitalization of $2.89 billion that same month. (It has since fallen in value to about $700 million, falling along with the rest of the biotech sector.)

Katiresan helped found Verve while he was a renowned cardiologist and geneticist at Harvard, where he discovered genetic mutations that caused people to have low cholesterol levels, protecting them from heart attacks.

Now he is trying to reproduce this phenomenon by turning off genes that increase cholesterol levels. Verve is developing drugs that target two genes. The first drug will target PCSK9, the second one will target ANGPTL3. Some patients will need only one of the drugs, while others will need both.

The company uses the Crispr DNA editing tool to change a single letter in the human genome. The lipid nanoparticle encapsulates the editing system to protect it on its way to the liver, where it turns off the desired gene.

The treatment showed encouraging results in monkeys, reducing bad cholesterol levels by 59% after two weeks and maintaining the effect after six months. Verve intends to start human trials within a few months; it will be years before the company has enough evidence of the drug’s safety and efficacy to consider obtaining regulatory approval.

Verve will face many obstacles in its attempt to treat the masses of people. This is one of the first experiences using Crispr to edit DNA inside the human body, and patients and clinicians may be wary of making permanent changes without knowing anything about long-term safety, says Elizabeth McNally, director of the Center for Genetic Medicine at Northwestern University’s Feinberg School of Medicine.

The reluctance to take Covid-19 vaccines suggests that some people do not want to change their DNA, she said.

Even if Verve can prove the drug is safe and effective for lowering bad cholesterol in people, it will have to convince insurers to buy it because it will almost certainly be more expensive than other options available, says Michael Sherman, chief medical officer at Point32Health Inc, a health insurance company.

Located in Canton, Massachusetts. “There has to be a reason for doing gene therapy to allow it, as opposed to just being newer and cooler,” he says.

Statins, the pill that was made available about 35 years ago to lower cholesterol levels, now cost as little as $9 for a month’s supply.

Introduced a few years ago, self-injecting drugs known as PCSK9 inhibitors, while better at lowering cholesterol than statins and requiring only once every few weeks, have yet to reach many patients, in part because they cost thousands of dollars a year.

Amgen Inc. and Regeneron Pharmaceuticals Inc., injection makers, have failed to convince insurers, even as they target people at high risk of familial hypercholesterolemia, despite more than doubling prices to $6,000 a year. In addition, some people are wary of self-injection.

So far, analysts predict Verve’s therapy will cost between $50,000 and $200,000 per patient. Companies rarely disclose pricing details before their products go to market, but Katiresan says the suggested range is a “reasonable starting point.”

Katiresan says that millions of people are not using existing treatments, and an infusion given to a young person can drastically change their risk for the rest of their lives.

This is something that could help his sibling, who died unexpectedly of a heart attack at the age of 42. “What worries me is that this is a response to a heart attack,” Katiresan says. “If it works.”


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