Verve 101: lowering cholesterol with a gene changing adenosine nanoparticles and guanine in the liver

But no one has ever used gene editing to lower cholesterol in people before. “This is a strategy that could be revolutionary,” said Karol Watson, a cardiologist at UCLA, during the news conference. “But we have to make sure it’s safe.”

VERVE- 101 consists of two RNA molecule packaged in a lipid object, one that changes adenine bases in the body, and another that recognizes PCSK9. After the treatment is injected, liver cells take up these nanoparticles, and once inside cells they make their way into the nucleii. Then, the base editor makes a single-letter change to the PCSK9 gene sequence, swapping an adenosine base with a guanine base. This turns off the gene and prevents liver cells from producing PCSK9 proteins.

Still, Verve’s share price plummeted by nearly 40% following the release of the results. Some researchers have suggested that the safety concerns are to blame, and say that gene therapies should be prioritized for conditions that have no available treatments.

Verve reported the findings, interim results from a phase 1b trial conducted in the United Kingdom and New Zealand, at a meeting of the American Heart Association in Philadelphia on 12 November. It will continue its trial next year in the United States, after receiving approval from the US Food and Drug Administration to enroll participants there.

The treatment came with some side effects: participants experienced brief flu-like symptoms, including fever, headaches and body aches, as well as a temporary increase in liver enzymes, which returned to normal within days.

First Verve Trial Results from the American Heart Association (AHEA) – An Update on Non-rare Gene Editing in Mice and Monkeys

The sentiment for editing when there are viable alternatives will be a challenge. Time will tell if non-rare is viable,” Michael Torres, cancer biologist and co-founder of genetic-medicines company ReCode Therapeutics, wrote in a post on X, formerly Twitter.

“From a scientific standpoint, there is still a lot of going in terms of addressing some of the key aspects of this technology,” says Luigi Naldini, a gene therapist at the Vita-Salute San Raffaele University in Milan, Italy. “The delivery by nanoparticles is still in early stages in terms of tolerability.”

Gene-editing approaches carry the risk of ‘off target’ edits elsewhere in the genome. The Verve team did not find any off-target editing in mice or the change in the PSCK9 gene in monkeys. Verve aims to select the best therapeutic dose from the trial next year and to launch a phase 2 trial in 2025.

The firm has to follow trial participants for 14 years as mandated by the FDA. “This is a gene editing study — you are changing the genome forever. Safety is going to be of the utmost importance, especially because there are currently safe and efficacious strategies available for lipid lowering,” said Watson at the press briefing.

The first patient was treated just six months ago, and researchers are still following all of the participants. The American Heart Association presented preliminary results at their annual meeting in Philadelphia.