- For the first time, a person has received a new type of gene editing treatment in a clinical trial, marking the latest research milestone in the rapid development of CRISPR technology into a powerful tool for altering human DNA to treat disease.
- The trial, run by the biotech company Verve Therapeutics, is testing a treatment for heart disease that relies on a newer and in theory more precise form of CRISPR known as base editing. Verve said Tuesday it had dosed the study’s first patient, about two months after receiving regulatory clearance for the trial in New Zealand.
- Verve plans to enroll about 40 patients with a form of heart disease known as hereditary familial hypercholesterolemia in the study, and aims to open up study sites in the U.S. and U.K. later this year. Initial results, which will focus on safety and changes in cholesterol levels, are expected sometime in 2023, Verve said.
Ten years ago last month, a paper describing a flexible method for altering DNA was published in the journal Science. Authored by Jennifer Doudna, Emmanuelle Charpentier and their colleagues, the paper showed how a bacterial immune system could be programmed to edit specific genes, giving researchers a potent new tool that in just a decade has reshaped genetic medicine.
Treatments built on the first generation of the gene editing technology, called CRISPR, have moved into human testing over the past few years and are delivering results that could lead to approved medicines. Already, though, a number of biotech companies are developing technologies that build on CRISPR, adapting it to make more targeted changes to DNA.
One of these newer technologies, called base editing, can change single “letters” in a gene without breaking both strands of the DNA double helix — a potentially safer and more efficient approach. Developed by David Liu at the Broad Institute of MIT and Harvard, base editing is being developed by Beam Therapeutics, which licensed use of the technology to Verve.
While Beam has secured Food and Drug Administration approval to begin testing in humans a base editing treatment for sickle cell disease, it doesn’t plan to enroll the first patient until later this year, leaving the milestone to Verve.
Verve’s treatment is designed to change an adenine, or an “A” letter, in an important gene known as PCSK9 to guanine, or “G.” That swap, Verve claims, will inactivate the PCSK9 gene, which helps control expression of a protein involved in absorbing LDL cholesterol. Higher levels of this protein should help lower cholesterol levels and thereby reduce heart disease risk.
Verve, which was started by the well-known cardiologist Sekar Kathiresan, has already shown its treatment can reduce PCSK9 and cholesterol levels in monkeys, and now aims to do the same in humans. The trial will have three parts, including an initial phase designed to determine the correct dose. Currently, investigators are enrolling patients at sites in Auckland and Christchurch, New Zealand, according to a federal database of clinical trials.
If testing proves out Verve’s hypothesis, the company’s treatment could offer a lasting way to lower cardiovascular risk with potentially a single infusion. Other drugs targeting PCSK9 are currently available, but are injected and must be taken chronically for life.