CRISPR Gene-Editing Therapy Shows Promise in Lowering Cholesterol
A recent small clinical trial has demonstrated that a CRISPR–Cas9 gene-editing therapy can cut cholesterol levels in participants by half. This finding raises hopes that, with further research, gene editing could serve as an effective treatment for a prevalent contributor to heart disease.
The researchers targeted a gene known as ANGPTL3, which plays a role in regulating fatty molecules like low-density lipoprotein (LDL) or ‘bad’ cholesterol and triglycerides in the bloodstream. Both of these molecules are associated with a higher risk of cardiovascular disease, and levels decreased by about 50% in participants who received the highest dose of the treatment.
So far, the therapy has been administered to just 15 individuals. However, if future studies yield positive results, the hope is that gene editing could eventually free countless people from the need to take daily cholesterol-lowering medications.
Luke Laffin, a preventative cardiology specialist at Cleveland Clinic and one of the trial’s lead investigators, expressed excitement about the potential impact. “What a revolution to be able to do that,” he remarked. “Conceptually, it’s a great idea: we can move from chronic therapy to something that’s one-and-done.”
Nonetheless, Laffin cautioned that fully realizing this vision could take years. More thorough safety evaluations will be necessary, and uncertainties remain regarding the treatment’s cost and public acceptance. The trial results, published in the New England Journal of Medicine on November 8, provide further evidence of the potential for gene-editing approaches to address some of the most widespread health concerns.
A Long-Awaited Vision
Kiran Musunuru, a cardiologist at the Perelman School of Medicine at the University of Pennsylvania, shared his aspirations for gene-editing therapies to become widely available. “The dream scenario for me is getting these gene-editing therapies broadly applied,” he stated. “These things are coming.”
Reflecting on a time just over a decade ago when he began to explore the use of CRISPR–Cas9 technology for preventing or treating cardiovascular disease, Musunuru recalled pitching the idea to various venture capitalists. “No one was interested at all,” he admitted, noting their preference for focusing on rare genetic disorders instead.
Now, he is aware of around a dozen companies aiming to use gene editing to address high cholesterol. Other projects in the cardiovascular realm include treatments for the rare condition transthyretin amyloidosis, which can result in heart failure. Notably, CRISPR Therapeutics, based in Zug, Switzerland and the sponsor of the current cholesterol trial, is also working on a gene-editing therapy to combat high blood pressure. Musunuru, who co-founded a company involved in similar treatment developments, referred to the landscape as “fertile ground.”
However, the transition from focusing on rare diseases to more prevalent conditions will necessitate extensive safety studies capable of identifying rare side effects, as CRISPR-based therapies have been tested on only a limited number of individuals thus far.
