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Remarkable and cautiously groundbreaking news in the medical world — after injecting human subjects with an experimental form of gene editing, researchers have achieved a dramatic reduction in the level of harmful cholesterol. This pioneering technique, known as base editing, has now been tested on humans for the first time and the results have been published in the prestigious science journal Nature.
However, it has not been without controversy. One participant in the study died after receiving the infusion, raising concerns about the safety of the treatment.
During the clinical trial, 10 individuals with genetically high levels of harmful cholesterol, also known as low-density lipoprotein (LDL), were administered an injection of VERVE-101, a gene-editing treatment utilizing the base editing technique. This treatment effectively turned off the gene for the PCSK9 protein, which is responsible for regulating LDL levels in the liver, potentially preventing coronary heart disease.
Base editing, which leverages CRISPR tools, enables precise alteration of specific gene sections without breaking or damaging DNA double strands, a significant improvement over previous gene-editing methods.
The results were promising, as participants saw their LDL levels reduced by up to 55% after 28 days. Prior to the trial, their average LDL levels were dangerously high at 193 mg/dL, well above the recommended threshold of less than 100 LDL, as per medical standards.
Even six months after the injection, individuals who received the higher dose of VERVE 101 experienced continued reductions in LDL levels.
“We don’t see that with the statin — we never see that much of a difference,” remarked University of Pittsburgh cardiologist Ritu Thamman to Nature, although Thamman was not involved in the clinical trial.
Nevertheless, the treatment is not without its drawbacks. Trial participants reported temporary chills, fever, and headaches reminiscent of a flu-like illness, along with a transient increase in liver enzyme levels.
Of the 10 patients, one died from a heart attack approximately five weeks after receiving VERVE-101, while another suffered a non-fatal heart attack a day after the injection. Nature reported a third-party safety panel’s claim that the fatal heart attack was not caused by VERVE-101, as the individual already had advanced heart disease.
The biotechnology company Verve Therapeutics is planning a phase 2 clinical trial of VERVE-101 in 2025, as reported by Nature.
VERVE 101 comprises two RNA molecules enclosed in a lipid nanoparticle. One molecule targets the PCSK9 gene, while the other edits the gene itself. When injected into a human subject, the package travels to the liver cell nuclei, where the RNA editing molecule precisely alters the PCSK9 gene, deactivating it and reducing the production of PCSK9 proteins, subsequently lowering LDL levels.
While this development is incredibly promising, there remain many unknowns regarding how gene editing will impact the human body. The research team plans to monitor surviving participants for the next 14 years to gain a clearer understanding of the long-term effects.
More on gene editing: Monkey Lives for Two Years With Gene-hacked Pig Kidney
