New drug successfully halts fibrosis in animal model of liver disease

A study published in the online journal Hepatology reports a potential new NADPH oxidase (NOX) inhibitor therapy for liver fibrosis, a scarring process associated with chronic liver disease that can lead to loss of liver function.

"While numerous studies have now demonstrated that advanced liver fibrosis in patients and in experimental rodent models is reversible, there is currently no for patients," said principal investigator David A. Brenner, MD, vice chancellor for and dean of the School of Medicine at the University of California, San Diego. "This new study provides important validation of the role of NOX in liver fibrosis, and suggests that a NOX inhibitor could provide an effective treatment for this devastating disease."

Most chronic liver diseases are associated with progressive fibrosis, which is triggered by the loss of and the activation of inadequate pathways. In addition, oxidative stress – which results from an inappropriate balance between the production and clearance of highly reactive molecules involved in cell signaling called reactive oxidative species (ROS) – leads to aberrant tissue repair in the liver.

When the liver is injured – for example, through hepatitis or alcohol abuse –HSCs are activated to become myofibroblasts, cells which play a crucial role in wound healing and the body's response to inflammation by recruiting immune cells called macrophages to the injury site. This process, triggered by intracellular signalling pathways involving NOX, can result in an abundance of scarring and eventually result in the loss of organ function.

By inhibiting NOX, the researchers theorized that myofibroblast activation and macrophage recruitment could be interrupted, preventing further fibrosis and potentially allowing regression of established fibrosis.

They assessed the effectiveness of treatment with GKT137831 – a NOX1/4 inhibitor developed by Genkyotex SA of Geneva, Switzerland – in mouse models, and found that treatment with this NOX inhibitor suppressed ROS production, as well as NOX and fibrotic gene expression.

"These data highlight the excellent pharmacological properties of GKT137831 and the broad potential for its use in fibrotic diseases,'' said Patrick Page, chief development officer at Genkyotex and contributor to the study.

According to Brenner, the next steps include a clinical trial with this drug in patients with .

add to favorites email to friend print save as pdf

Related Stories

Scarring cells revert to inactive state as liver heals

May 07, 2012

An international team of scientists, led by researchers at the University of California, San Diego School of Medicine, report that significant numbers of myofibroblasts – cells that produce the fibrous ...

New study upends thinking about how liver disease develops

Dec 20, 2010

In the latest of a series of related papers, researchers at the University of California, San Diego School of Medicine, with colleagues in Austria and elsewhere, present a new and more definitive explanation of how fibrotic ...

Scientists Uncover Protective Mechanism Against Liver Cancer

Dec 14, 2009

(PhysOrg.com) -- A team of scientists from the UC San Diego School of Medicine and Osaka University in Japan have identified a protein switch that helps prevent liver damage, including inflammation, fibrosis and cancer. The ...

Recommended for you

A multiscale approach to Ebola response

8 minutes ago

The Ebola outbreak in western Africa continues to spread uncontrolled, affecting thus far five countries. On September 16th, President Obama spoke at the Centers for Disease Control and Prevention headquarters ...

Overwhelmed west Africa ramps up Ebola response

14 hours ago

West Africa intensified its response to the deadly Ebola epidemic on Sunday, with Sierra Leone uncovering scores of dead bodies during a 72-hour shutdown and Liberia announcing hundreds of new hospital beds.

Sierra Leone reaches final day of Ebola lockdown

18 hours ago

Frustrated residents complained of food shortages in some neighborhoods of Sierra Leone's capital on Sunday as the country reached the third and final day of a sweeping, unprecedented lockdown designed to ...

Sierra Leone faces criticism over Ebola shutdown

Sep 20, 2014

Sierra Leone began the second day of a 72-hour nationwide shutdown aimed at containing the spread of the deadly Ebola virus on Saturday amid criticism that the action was a poorly planned publicity stunt.

Presence of peers ups health workers' hand hygiene

Sep 19, 2014

(HealthDay)—The presence of other health care workers improves hand hygiene adherence, according to a study published in the October issue of Infection Control and Hospital Epidemiology.

User comments