New therapy targets the liver's PCSK9 gene to lower cholesterol
By Bronwyn Thompson
https://newatlas.com/author/bronwyn-thompson/A
new CRISPR-based one-off procedure that lowers "bad" cholesterol is
expected to enter Phase I human trial in 2026. 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 millionper
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