Scientists tested a new way to fix liver cells in mice with familial hypercholesterolemia, a genetic condition that causes dangerously high cholesterol. They used a technique called electroporation to deliver gene-editing tools into liver cells, then used a medicine to help the edited cells survive and multiply. While this approach worked better than previous methods at getting edited cells into the liver, it didn’t actually help reduce cholesterol buildup in blood vessels or prevent fatty liver disease. The study shows that the same gene-editing strategy that worked for one liver disease didn’t work for another, suggesting doctors will need to customize treatments for different genetic conditions.

The Quick Take

  • What they studied: Whether a new method of delivering gene-editing tools into liver cells could help treat familial hypercholesterolemia (a genetic condition causing very high cholesterol)
  • Who participated: Laboratory mice genetically engineered to have familial hypercholesterolemia, compared to normal mice
  • Key finding: The gene-editing technique successfully got edited cells into the liver (up to 13% of liver cells), and these cells did reduce cholesterol and triglycerides in the blood by 18% and 52% respectively. However, this didn’t prevent heart disease or fatty liver from developing, and fat accumulated in the liver over time.
  • What it means for you: While this gene-editing approach shows promise for delivering edited cells to the liver, it may not be the right solution for familial hypercholesterolemia. The research suggests that different genetic liver diseases may need different treatment strategies rather than using the same approach for all conditions.

The Research Details

Researchers used a technique called electroporation, which uses electrical pulses to open tiny holes in cell membranes and let gene-editing tools inside. They applied this method to liver cells from normal mice and inserted them into mice with familial hypercholesterolemia. To help the edited cells survive and grow, they gave the mice a temporary dose of acetaminophen (a common pain reliever), which creates conditions where edited cells have an advantage over normal cells.

They compared two groups: mice that received the acetaminophen treatment and mice that didn’t. They then measured how many edited cells stayed in the liver, how much cholesterol and triglycerides were in the blood, and whether the mice developed heart disease and fatty liver disease.

This approach was based on previous success treating a different genetic liver disease called phenylketonuria. The researchers wanted to see if the same strategy would work for familial hypercholesterolemia.

Electroporation delivers gene-editing tools more efficiently than previous methods, meaning more cells get edited. Understanding whether this improved delivery method can actually treat genetic diseases is crucial for developing real treatments. This study also reveals an important principle: just because a treatment works for one genetic liver disease doesn’t mean it will work for another, which helps guide future research.

This is a controlled laboratory study using genetically engineered mice, which allows researchers to test the approach in a controlled setting. The study included proper control groups (mice without treatment) for comparison. However, results in mice don’t always translate to humans, and the sample size details weren’t fully specified. The findings were statistically significant (p = 0.0121), meaning the results were unlikely due to chance.

What the Results Show

The electroporation method successfully delivered gene-editing tools to liver cells. In mice that received acetaminophen treatment, about 13% of liver cells became edited cells, compared to only 2% in mice without the treatment. This shows the acetaminophen helped edited cells survive and multiply.

The edited cells did have some positive effects: they reduced LDL cholesterol (the “bad” cholesterol) by 18% and triglycerides by 52% compared to untreated mice. These are meaningful improvements in blood lipid levels.

However, these improvements didn’t translate to preventing disease. The mice still developed atherosclerosis (hardening of arteries) and fatty liver disease at similar rates to untreated mice. Additionally, fat accumulated in the livers of treated mice over time, even after the acetaminophen treatment stopped.

The liver damage markers (signs of injury) returned to normal after stopping acetaminophen, which is good news for safety. However, the persistent fat accumulation in the liver suggests that the edited cells were causing problems with how the liver handles cholesterol, even though they were reducing cholesterol in the blood. This unexpected side effect was the key reason the treatment didn’t work as hoped.

This approach had previously worked well for phenylketonuria, another genetic liver disease, where edited cells could compensate for the genetic defect. However, in familial hypercholesterolemia, the edited cells couldn’t fully compensate, and actually created new problems with cholesterol handling in the liver. This shows that the same gene-editing strategy doesn’t work equally well for all genetic liver diseases.

The study was conducted only in mice, and results may not directly apply to humans. The exact number of mice used wasn’t clearly specified. The study only tested one specific gene-editing approach, so other methods might work better. The mice were only observed for 5 weeks after treatment, so long-term effects remain unknown. Additionally, the study didn’t test whether different doses or timing of acetaminophen might improve results.

The Bottom Line

Based on this research, electroporation-mediated gene editing with acetaminophen selection is NOT recommended as a treatment for familial hypercholesterolemia at this time (confidence level: moderate to high). However, electroporation itself appears to be a useful tool for testing other gene-editing approaches for liver diseases. Researchers should explore different genes to edit or different selection strategies for familial hypercholesterolemia treatment.

People with familial hypercholesterolemia and their families should be aware that while gene-editing research is advancing, this particular approach didn’t work as hoped. Researchers and pharmaceutical companies developing genetic treatments should note that successful strategies for one disease may not work for another. Healthcare providers should continue recommending current treatments (statins, other cholesterol medications) for familial hypercholesterolemia patients.

This research is still in early laboratory stages. Even if a better gene-editing approach is found, it would typically take 5-10 years of additional testing before human trials could begin, and several more years before any treatment might become available to patients.

Want to Apply This Research?

  • Users with familial hypercholesterolemia should track their LDL cholesterol and triglyceride levels monthly (via blood tests ordered by their doctor) to monitor how well their current treatment is working, and note any changes when new treatments become available.
  • Continue taking prescribed cholesterol medications as directed. Use the app to set reminders for medication doses and to log cholesterol test results. Track dietary choices (especially saturated fat intake) since diet significantly impacts cholesterol levels in familial hypercholesterolemia.
  • Establish a baseline of current cholesterol levels, then monitor quarterly blood work results through the app. Create alerts for when cholesterol levels rise above target ranges. Share this data with healthcare providers to guide treatment decisions as new therapies become available.

This research describes early-stage laboratory studies in mice and does not represent an approved or available treatment for familial hypercholesterolemia. People with familial hypercholesterolemia should continue following their doctor’s current treatment recommendations, which typically include cholesterol-lowering medications and lifestyle changes. Do not stop or change any prescribed medications based on this research. Consult with your healthcare provider or a genetic specialist before making any decisions about your cholesterol treatment plan. Gene-editing therapies for human use are still in development and not yet available for this condition.