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Researchers were able to drastically reduce the level of bad cholesterol in humans after injecting them with an experimental gene-editing treatment, according to the scientific journal Naturewhich is the first time this technique, called base editing, has been performed on humans.
But at least one person has died after receiving an infusion, raising a number of safety concerns.
In the clinical trial, 10 individuals with congenitally high levels of bad cholesterol, also known as low-density lipoprotein (LDL), received an injection of VERVE-101, a gene-editing treatment that uses the basic editing technique. This treatment then disabled the gene for the PCSK9 protein, which is found in the liver and regulates LDL. High LDL levels can lead to coronary heart disease.
Base editing takes advantage of CRISPR tools to change or edit specific portions of a gene in precise movements that prevent DNA double-strand breaks, unlike previous gene editing techniques.
The results were promising, with trial participants seeing their LDL reduced by up to 55% after 28 days. Before the experiment, they had an average LDL of 193 mg/dL, which is extremely high and can be fatal. People should have less than 100 LDL, according to medical standards.
Six months after the injection, participants who received a high dose of VERVE 101 still had lower LDL levels.
“We don’t see that with the statin — we never see much of a difference,” Ritu Thamman, a cardiologist at the University of Pittsburgh in Pennsylvania, told Nature. Thamman was not involved in the clinical trial.
But the treatment has disadvantages. Study participants reported a brief bout of chills, fever and headaches – as if they had the flu, as well as a transient increase in liver enzyme levels.
And of the 10 patients in the trial, one subject died of a heart attack about five weeks after receiving VERVE-101, while a second participant had a non-fatal heart attack the day after the injection. Nature reported that a safety panel made up of third-party experts said the fatal heart attack was not due to VERVE-101 and that they were already suffering from “advanced heart disease.”
Boston, Massachusetts biotechnology company Verve Therapeutics plans to launch a phase 2 clinical trial of VERVE-101 in 2025, according to Nature.
VERVE 101 is composed of two RNA molecules inside a lipid nanoparticle, according to Nature. One molecule sniffs out the PCSK9 gene while the other RNA edits the gene itself. When VERVE 101 is injected into a human test subject, the package travels to the nuclei of liver cells, where the RNA editing molecule makes a precise change to the PCSK9 gene, altering one of its nucleotide bases. This movement causes the PCSK9 gene to be deactivated and, therefore, the liver stops producing PCSK9 proteins, causing a reduction in LDL levels.
The work could be innovative, i.e. – But there are also many unknowns about how gene editing will affect the rest of the human body. The research team will follow the surviving test subjects for the next 14 years to find out.
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