Researchers created a new experimental drug called MHY5396 that works by activating two different pathways in the body that help control inflammation and fat metabolism. In laboratory and animal studies, this drug reduced scarring (fibrosis) in the liver and kidneys, decreased fat buildup in the liver, and improved overall organ health. The drug was well-absorbed when taken by mouth and showed effects similar to or better than existing fibrosis treatments. While these results are exciting, the drug has not yet been tested in humans, so it’s too early to know if it will work the same way in people.

The Quick Take

  • What they studied: Whether a new experimental drug (MHY5396) could reduce organ scarring and improve how the body handles fat by activating two specific cellular switches (FXR and PPARα)
  • Who participated: Laboratory studies used human liver and kidney cells, plus mice with artificially induced liver and kidney scarring to mimic human disease
  • Key finding: MHY5396 successfully reduced scarring in both liver and kidney tissues and decreased fat accumulation in liver cells, performing as well as or better than an existing approved fibrosis drug
  • What it means for you: This research suggests a potential new treatment approach for organ scarring diseases, but it’s still in early stages and hasn’t been tested in humans yet. People with fibrosis should continue following their doctor’s current treatment plans while researchers work toward human trials.

The Research Details

This was a laboratory and animal research study designed to test a new experimental drug. Scientists first tested MHY5396 in human liver and kidney cells grown in dishes to see if it could activate two important cellular switches called FXR and PPARα. They then tested the drug in mice that had been given chemicals or special diets to create scarring in their livers and kidneys, mimicking what happens in humans with fibrotic diseases. The researchers measured how well the drug was absorbed and processed by the body when given orally (by mouth) to the mice. They compared MHY5396’s effects to an existing approved drug called obeticholic acid to see if the new drug worked better, worse, or about the same.

This research approach is important because it tests a completely new strategy for treating scarring diseases. Instead of just targeting one pathway in the body, this drug targets two pathways at once, which could be more effective. Testing in both cells and animals helps researchers understand how the drug works before it ever reaches human testing. The pharmacokinetic studies (how the body processes the drug) are crucial because a drug only helps if the body can absorb and use it properly.

This study was conducted by experienced researchers and published in a peer-reviewed journal, which means other scientists reviewed the work. However, this is still early-stage research using laboratory cells and animals, not humans. The results are promising but preliminary. The study was well-designed with appropriate controls and comparisons to existing treatments, which strengthens the findings. The fact that the drug worked in two different disease models (liver and kidney) suggests the effects may be real and not just luck.

What the Results Show

MHY5396 successfully activated both FXR and PPARα in human liver cells, with particularly strong activation compared to other similar compounds tested. In liver cells, the drug reduced the amount of fat being made and increased the breakdown of existing fat, leading to less fat accumulation overall. When tested in mice with liver scarring from a special diet lacking methionine and choline, MHY5396 reduced fat buildup, decreased liver damage markers, and reduced scarring. In mice with scarring caused by thioacetamide (a chemical that damages the liver), MHY5396 reduced scarring to a degree similar to obeticholic acid, which is an approved drug for certain liver diseases. The drug was well-absorbed when given by mouth, with 98.6% of the dose reaching the bloodstream, and it was primarily broken down by the liver with very little being lost through urine.

Beyond liver effects, MHY5396 also showed significant benefits in kidney cells and in mice with kidney scarring caused by folic acid. The drug reduced both inflammation and scarring in kidney tissue. This suggests the drug’s benefits may extend beyond the liver to other organs affected by scarring. The drug’s safety profile appeared good in these studies, with no major toxicity concerns noted, though long-term safety studies in humans would still be needed.

Obeticholic acid, an existing approved drug that activates FXR, is used to treat certain liver diseases. MHY5396 performed comparably to obeticholic acid in reducing liver scarring, which is impressive because MHY5396 activates two pathways instead of one. This dual-action approach may offer advantages over single-pathway drugs, though this would need to be confirmed in human studies. The ability to reduce both scarring and fat accumulation addresses two problems that often occur together in liver disease, which previous single-target drugs haven’t done as effectively.

This research was conducted entirely in laboratory cells and animals, not in humans. Results in mice don’t always translate to humans due to differences in metabolism and disease complexity. The study didn’t test long-term effects or potential side effects that might emerge with extended use. No human safety or effectiveness data exists yet. The study also didn’t compare MHY5396 to all other available fibrosis treatments, only to obeticholic acid. The exact doses and treatment durations used in mice may not translate directly to what would be used in humans.

The Bottom Line

Based on this early research, MHY5396 shows promise as a potential future treatment for organ scarring diseases, but it is not yet available for human use. Current confidence level: Low to Moderate (this is preliminary research). People with fibrosis should continue working with their doctors on proven treatments. Researchers should proceed with human clinical trials to determine if these promising laboratory results translate to real benefits in patients.

This research is most relevant to people with liver or kidney scarring (fibrosis), their families, and healthcare providers treating these conditions. Researchers and pharmaceutical companies developing new fibrosis treatments should also pay attention. People without fibrosis don’t need to take action based on this research. Those currently taking fibrosis medications should not change their treatment based on this preliminary study.

Since this is early-stage research, human clinical trials would likely take several years to complete if the drug moves forward. Even if trials are successful, it could be 5-10 years before MHY5396 might become available as a treatment. People shouldn’t expect this drug to be available soon, but it represents promising progress in fibrosis research.

Want to Apply This Research?

  • For people with fibrosis currently using the app: Track liver function test results (ALT, AST, bilirubin) and fibrosis markers (FIB-4 score, AST-to-platelet ratio) every 3-6 months as recommended by your doctor. Note any changes in fatigue, abdominal swelling, or other symptoms. This baseline data will be valuable if you ever participate in clinical trials for new treatments.
  • While waiting for new treatments to be developed, users can focus on lifestyle factors that support liver and kidney health: maintain a healthy weight, limit alcohol consumption, stay hydrated, eat a balanced diet low in processed foods, and exercise regularly. Users can set reminders to take current medications as prescribed and attend all scheduled doctor appointments to monitor disease progression.
  • Create a long-term health tracking system that records liver and kidney function tests, fibrosis progression markers, weight, and symptom severity. Set quarterly check-in reminders to review trends with your healthcare provider. This ongoing monitoring helps identify if current treatments are working and provides important data if clinical trials for new drugs like MHY5396 become available in your area.

This research describes an experimental drug (MHY5396) that has only been tested in laboratory cells and animals, not in humans. It is not approved by any regulatory agency and is not available for human use. This article is for educational purposes only and should not be interpreted as medical advice. People with liver or kidney scarring should continue following their doctor’s current treatment recommendations. Do not attempt to obtain or use this experimental drug outside of an approved clinical trial. Always consult with your healthcare provider before making any changes to your treatment plan. The findings presented here are preliminary and may not translate to human benefit.