NIH scientists synthesize drug that limits liver fibrosis in mice

Liver fibrosis is a progressive scarring of the liver brought on by chronic alcoholism, viral hepatitis, obesity or diabetes. The condition could lead to cirrhosis and cancer of the liver. Despite its prevalence, there is no mainstay treatment to prevent scarring.

Now researchers at the National Institutes of Health (NIH) have reported developing a drug that limits liver fibrosis in mice. The findings have been published online in the journal JCI Insight.

The drug was synthesized using the chemical structure of ibipinapant--a brain-penetrating CB-1 receptor antagonist--as the backbone for the drug with two changes to it.

CONFERENCE

AI Innovations for Life Science and Healthcare Summit East

Join the expert speaking faculty of over 30 life science, healthcare, and tech professionals on June 13–14, 2019, in Philadelphia, as we elevate clinical trial operations, healthcare outcomes, and supply chain implementation through AI. Use Discount Code 796819FIERCE to save 15% off the standard registration rate.

First they altered the structure to lower the amount that can pass the blood-brain barrier. This avoided any psychiatric side effects that limit the use of the original drug, ibipinapant, in the clinic. Secondly, they added a molecular group that inhibits the molecule iNOS, an enzyme responsible for promoting inflammation.

“Inducible nitric oxide synthase, or iNOS, is an enzyme that has been shown to play a fundamental role in liver fibrosis pathology and is a potential target for fibrosis therapy,” said George Kunos, who heads the study, in an NIH news release. “It is also an important factor in alcoholic liver disease, viral hepatitis, fatty liver disease, and other pathologies that promote liver fibrosis.”

In two well-established models of liver fibrosis, the NIH group found that their compound worked better to reduce fibrosis than using either CB-1 receptor inhibition or iNOS delivery alone.

Preliminary studies in their lab demonstrate no “off target” effects that might give rise to side effects, at least in their animal models. Kunos admits that the compound will need to be further tested in animal models before it's taken forward to clinical trials.

- here is the release
- get the journal abstract

Related Articles:
Intercept shares dazzle after early success of PhIIb liver disease drug trial
Biomarkers spot hep C liver disease

Suggested Articles

Maryland researchers discovered a type of stem cell in hair follicles that can rebuild the myelin that breaks down in brain diseases like multiple sclerosis.

Three weeks after filing luspatercept for FDA approval, Celgene has submitted the anemia drug for consideration by the European Medicines Agency.

AliveCor has secured two additional FDA clearances for its personal electrocardiogram, allowing it to detect bradycardia and tachycardia arrhythmias.