A recent small trial of a cholesterol-lowering treatment based on CRISPR gene editing has shown promising results, but safety concerns have been raised. The trial involved 10 individuals with an inherited disease that leads to high cholesterol levels and an increased risk of heart disease. The treatment, developed by Verve Therapeutics in Boston, aims to be a one-time solution that could potentially replace traditional cholesterol-lowering drugs like statins.
The trial showed that the treatment effectively lowered LDL cholesterol levels, which are associated with heart disease risk, by 39 to 55 percent in the three participants who received the highest doses. However, one of these individuals experienced a heart attack the day after the treatment, raising concerns about its safety. Verve Therapeutics has stated that the heart attack could potentially be related to the treatment, but it could also be attributed to the participant's underlying disease.
The company plans to conduct further small trials of the higher dose levels in the UK and New Zealand, and if successful, a larger randomized controlled trial will be conducted to gather more definitive evidence on the safety issue. Verve Therapeutics is using a variant of CRISPR gene editing known as base editing, which involves modifying CRISPR enzymes to change specific DNA letters without cutting the DNA. This reduces the risk of unwanted mutations, although it does not eliminate it entirely.
Unlike previous CRISPR treatments that involve removing cells from the body, modifying them, and reintroducing them, Verve's treatment involves injecting the CRISPR machinery into the body using lipid nanoparticles. This method is similar to the mRNA COVID-19 vaccines and could potentially make the treatment more affordable and widely available if proven safe.
The lipid nanoparticles are primarily taken up by liver cells, which then produce a protein that disables a gene responsible for a protein called PCSK9. PCSK9 breaks down an enzyme that removes cholesterol from the blood, so disabling it lowers cholesterol levels. Some individuals naturally have mutations that disable PCSK9 and are less likely to develop heart disease.
While this initial trial was small, the significant reductions in cholesterol observed in participants who received higher doses suggest that the treatment is effective. However, more research is needed to address safety concerns and determine the long-term effectiveness of the treatment. This milestone in the field of gene editing has been hailed as important by experts in the field.