A new CRISPR-based one-off procedure that lowers "bad" cholesterol has been approved to enter Phase I human trial. If successful, it could be the first approved genetic-silencing method on the market, replacing the need for long-term medication and slashing the risk of cardiovascular disease.
There are high hopes for US biotech company Scribe Therapeutics' STX-1150 treatment, which epigenetically silences the PCSK9 gene in the liver to reduce low-density lipoprotein cholesterol (LDL-C). This is, of course, not the first of its kind – we wrote about Verve Therapeutics' effort in 2023 and CRISPR Therapeutics' CTX310 candidate more recently. However, they're both still in their trial stages.
STX-1150 targets hypercholesterolemia, a key driver of atherosclerotic cardiovascular disease (ASCVD). It epigenetically silences PCSK9 to reduce LDL-C without making any permanent DNA changes.
"We designed STX-1150 to overcome many of the limitations of today’s lipid-lowering therapies through powerful epigenetic silencing, and to meaningfully change how cardiovascular risk is managed for millions of patients," said Scribe CEO Dr. Benjamin Oakes.
Instead of cutting or permanently altering DNA, STX-1150 essentially installs modifications and DNA methylation marks at the PCSK9 locus in liver cells, which silences gene expression in a way that can be reversed if needed.
In the field of medical science, CRISPR is still in its infancy – major breakthroughs were seen in 2019, and last year it was used for the first time to successfully treat a baby with an incurable genetic illness. In 2024, the US Food and Drug Administration (FDA) approved a groundbreaking CRISPR/Cas9 therapy for sickle cell disease, showing just how quickly the technology is advancing. And while this precision medicine is seen by many as the future of disease treatment, it still faces a lot of regulatory and ethical challenges.
It also faces accessibility hurdles – the sickle cell disease therapy Casgevy costs an estimated US$2.2 million per patient, which is out of reach of most of us. A successful treatment for cardiovascular disease would remove the cost of ongoing medication to manage conditions such as high LDL-C, but the question remains whether the 70 million Americans estimated to have chronically high cholesterol would have access to this one-off therapy once approved.
That said, penicillin wasn't cheap when it first hit the market in 1940, costing the equivalent of around $400 per dose. And an approved CRISPR therapy for LDL-C has the potential to be the first of many such treatments that shift its accessibility. After all, biotechnology and personalized medicine is considered to be the future of medicine. We just have to get there first.
"Entering the clinic with STX-1150 represents a defining moment for Scribe and the wider genetic medicine field,” said Oakes. "Scribe has been engineering CRISPR-based medicines with the potency, specificity, and durability profile that can elevate the current standard of care, particularly for large cardiometabolic populations."
Source: Scribe Therapeutics
