- Researchers are reporting that two new treatments can effectively target cholesterol at the genetic level.
- Both treatments are aimed at people with a genetic predisposition to high cholesterol for whom diet and exercise aren’t effective.
- Experts note that both treatments need more research and likely won’t be ready for approval for years.
Two promising new clinical trials aimed at the genetics of cholesterol were unveiled this week at the American Heart Association’s
Both drugs, designed to drive down unhealthy levels of cholesterol were shown to be effective and safe, their creators said.
The medications target people born with a genetic predisposition to high cholesterol, increasing the user’s odds of heart attacks and stroke.
Current tools to manage high cholesterol include exercise, diet, and statin medications. These two new drugs would be the first to go after the genetic cause of high cholesterol.
However, neither will hit the market anytime soon, as both will require years of more research before being approved for consumers.
Nonetheless, experts say the results are encouraging.
“The new studies… are really a groundbreaking change in the world of cardiovascular medicine,” said Dr. Spencer Kroll, a physician with the Kroll Medical Group and the Cholesterol Treatment Center in New Jersey and a director of the Northeast Lipid Association.
“Even though they’re in early-stage clinical trials, these studies represent that cholesterol management and cardiovascular disease treatment is a multimodal and individualized process,” Kroll, who was not involved in the research, told Medical News Today. “We are now entering the realm of cholesterol therapy that moves away from the one-size-fits-all statin treatment to therapies that are personalized to the individual patient.”
It’s given through an IV and targets the PCSK9 gene, which is associated with higher levels of LDL, also known as “bad cholesterol.”
Researchers explain that the drug makes a tiny change to PCSK9, limiting its ability to raise cholesterol. Theoretically, a one-timetreatment should last a lifetime, although test subjects have so far only been followed for six months.
The initial study only had 10 participants and was meant to look at the drug’s safety. Most of the subjects didn’t receive doses big enough to make a measurable difference in cholesterol levels but got through the trial without major side effects or health issues.
The Verve Therapeutic researchers report they did give higher doses to three subjects, whose LDL levels were reduced by more than half.
All the study participants had a genetic condition called
“Although this first-in-human trial was very small, it did show a large drop in LDL levels in a few patients,” said Dr. Cheng-Han Chen, an interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in California who was not involved in the research.
“Most importantly, the study was successful in showing that the “base editing” technique can work in the liver in humans,” Chen told Medical News Today. “These are very initial clinical results that show proof-of-concept in humans, but that require much more research before they can be used on a wider scale.”
The research on this drug has not been published yet in a peer-reviewed journal.
A second, potentially groundbreaking therapy aimed at reduced cholesterol was also
This one targets a type of protein associated with cholesterol called lipoprotein. People with high levels of lipoprotein(a) are at high risk of fats and cholesterol building up in their arteries. Lipoprotein clings to LDL cholesterol, potentially causing a build-up of plaque.
The condition is genetic and researchers noted exercise, diet, and statins have little impact on lipoprotein levels.
The research team, which was financed by drug company Eli Lilly, used a drug called lepodisiran, which helps block the production in the level of a key protein component of lipoprotein(a) particle.
The second study was also small – just 48 adults in the United States and Singapore with high levels of lipoprotein(a).
Researchers reported the drug was found to be safe with no major side effects. They said the medication also reduced lipoprotein(a) levels by 94% for a year with a single dose.
Researchers noted that 64 million adults in the United States have elevated lipoprotein levels.
Experts who were not involved in the research told Medical News Today that although the study results are promising, both treatments have a long way to go.
“While this small proof of concept study of VERVE-101 is highly interesting, I would presume that many hundreds if not thousands of similar patients would need to be treated to show the safety and effectiveness of this therapy before the Food and Drug Administration or other international regulatory bodies would consider approval,” said Dr. Wesley Milks, a cardiologist who specializes in cardiovascular disease prevention, including management of lipid disorders, at the Ohio State University Wexner Medical Center.
Milks said there are potential downsides with treating people at the genetic level.
“With an intervention that results in theoretically permanent DNA editing, the irreversibility of such therapy could be off putting to many patients and healthcare providers,” he noted. “I certainly would want to be quite sure that off-target or other untoward genetic disturbances would be extremely unlikely as a result of receiving this CRISPR gene editing therapy before recommending it to my own patients.”
In addition, the treatments, when finally approved, might have other downsides, said Dr. Rekha Kumar, the chief medical officer of weight loss program Found and former medical director of the American Board of Obesity Medicine.
“This is novel due to the mechanism of action of these two new potential drugs, but both are far from everyday use,” Kumar said. “Both target specific genetic abnormalities related to cholesterol metabolism, making it a significant development as we move in the direction of personalized therapies for disorders of cholesterol metabolism.”
“When drugs get this personalized, they get very expensive, so we are talking about a high cost for a drug that treats a specific population,” she added. “Often, many people don’t know they have these disorders or have access to the right care to get tested for these genetic abnormalities.”