A new study, now published in the journal Nature Biotechnology, posits that people who are at a high risk of heart disease due to their excessive levels of cholesterol may soon have a safe and effective alternative treatment in gene editing.
Most people with hypercholesterolemia take statins to treat their condition, but for others, these drugs are not enough to lower their cholesterol.
According to some research, 1 in 7 people with inherited hypercholesterolemia might have to resort to another type of drug called PCSK9 inhibitors.
However, treatment with PCSK9 inhibitors may often be inconvenient because it requires repeated injections, and some patients simply do not tolerate the drug.
For these people, gene editing may be the solution, according to new research from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
Cholesterol lowered by 30–60 percent
In a healthy body, the PCSK9 gene breaks down low-density lipoprotein (LDL) receptors that are responsible for removing excess cholesterol from our blood.
PCSK9 inhibitors help to lower levels of LDL, or "bad," cholesterol. But for people who do not tolerate these drugs, Wang and colleagues have found a workaround.
"Most often," explains Wang, "these patients are treated with repeated injections of an antibody to PCSK9 [...]."
"But, our study shows that with successful genome editing, patients who cannot tolerate inhibitor drugs might no longer need this type of repeat treatment."
The researchers designed an enzyme that targets and deactivates the PCSK9 gene. They used an
Animals that received the treatment were found to have lower PCSK9 and LDL cholesterol levels.
Specifically, the middle and high doses of the treatment decreased PCSK9 levels by 45–84 percent and cholesterol levels by 30–60 percent.
These AAV vector doses were previously shown to be safe and effective in human clinical trials of gene replacement therapy for treating hemophilia.
"Our initial work with several delivery and editing approaches," notes senior study author Dr. James M. Wilson, who is the director of the Gene Therapy Program at the university, "produced the most impressive data in nonhuman primates when we paired AAV for delivery with the engineered [enzyme] for editing."
"We leveraged," he goes on to say, "our 30-plus years of experience in gene therapy to progress the translational science of in vivo genome editing, and in doing so, reinforced the importance of early studies in nonhuman primates to assess safety and efficacy."