CRISPR revolution nears mainstream cardiovascular care
The evolving technology is expected to become a cornerstone of medicine and transform how numerous diseases are treated.
CRISPR technologies are moving from the lab to late-stage clinical trials, potentially transforming the treatment of cardiovascular disease, rare genetic disorders and other chronic conditions.
“It's research now, but it's not going to be research for much longer. There's no question, these kinds of therapies are working in patients in clinical trials, and they are going to get approved,” said Kiran Musunuru, MD, PhD, MPH, ML, MRA, FAHA. “We’ll have to be a little patient and wait a few years, but they're going to be approved, and they're going to transform the practice of medicine.”
Musunuru is among the speakers at the Saturday session “The Future Is Now: Gene Therapy for Cardiovascular Disease” who will offer insight and examples of this impact on cardiovascular health. Musunuru is the Barry J. Gertz Professor for Translational Research at the University of Pennsylvania Perelman School of Medicine in Philadelphia.
CRISPR technology has evolved significantly beyond its original form, Musunuru said. Early gene editing methods focused on cutting DNA to disable harmful genes, but newer approaches enable scientists to precisely change individual DNA letters, rewrite sections of genetic code or regulate gene activity without altering the underlying sequence.
CRISPR’s key advantage today is its programmability, he said. Researchers can redirect the technology to different genes by changing a short segment of guide RNA, which acts as a molecular GPS system and directs the editing machinery to a specific location within the genome.
Take, for example, the gene involved in the serious and often fatal condition transthyretin amyloidosis. In one of the most advanced applications of CRISPR technology, Musunuru said, a phase 3 gene-editing trial has suggested that the therapy permanently turns off the disease-causing gene, TTR, after a single treatment. The therapy uses lipid nanoparticles to deliver CRISPR directly to liver cells and could potentially offer lifelong protection from the condition, he said.
“This trial has gotten a lot of interest recently because now there are therapies for this disease for the first time — in just the past 10 to 15 years. Before, it was untreatable, and it was uniformly fatal. But now we have treatments that don’t just improve the disease but improve life expectancy,” Musunuru said.
“The premise is that when you turn off a gene at the DNA level, it's permanently off; it's off forever. So, if you receive this treatment once, you are protected for the rest of your life.”
The same platform has also been adapted to treat hereditary angioedema, a disease characterized by dangerous swelling attacks. By altering the genetic “GPS” component of the therapy, researchers redirected CRISPR to KLKB1, the gene responsible for the condition. According to Musunuru, clinical trial results have shown the treatment can effectively eliminate disease episodes, offering a potential one-and-done therapy for patients who currently live with ongoing risk.
One of the most promising cardiovascular applications of today’s CRISPR technology is treating high cholesterol and atherosclerotic cardiovascular disease, Musunuru said. Clinical trials targeting PCSK9 and ANGPTL3, genes that influence cholesterol levels, show promise so far. For example, he said, early data show that a single treatment targeting PCSK9 can reduce LDL cholesterol by approximately 60% with effects that appear durable over time.
Although the focus of Musunuru’s presentation will be on cardiovascular applications, he said the technology has the potential to revolutionize the care of other chronic diseases, including the rare inherited disorder phenylketonuria and fatty liver disease, and change the way we look at preventive healthcare in younger people. In the future, healthy people at elevated cardiovascular risk could potentially receive a one-time therapy that provides decades of protection against heart attacks and strokes, he said.
“By being able to change a few letters, this technology allows us to think about drug development in a very different way. Everyone in the room should get ready for the day they'll be prescribing these therapies. And they should have some understanding of how it works and what it does,” Musunuru said.
“It will be like antibiotics. It will be so routine that it's just part of the standard of care. It’s going to be a mainstay of medicine.”
