Researchers from the Experimental Hepatology and Gene Therapy Laboratory of the IIMT – Austral University / CONICET, in Argentina, identified that the RAC1 protein can be blocked pharmacologically, reducing liver damage in cases of fulminant hepatitis.

This discovery, unprecedented worldwide, opens a new therapeutic route for a disease with very few options, with the particularity of being based on a molecule that was originally designed for oncology.

Fulminant hepatitis and other liver diseases are global public health problems, with approximately 2 million deaths annually. The therapeutic potential of this research could lead to new and effective solutions to these challenges.

Also known as severe acute liver failure, fulminant hepatitis is a disease that can cause death in up to 40% of cases if a transplant is not performed in time.

Research Results

The study, recently accepted for publication in the Journal of Hepatology Reports, demonstrates that the inhibition of RAC1 proteins, through a specific molecule (1D-142), generates a protective effect on the liver, reducing inflammation, cellular necrosis and biochemical markers of damage.

Preclinical trials, carried out in three animal models, revealed a significant decrease in liver damage and an increase in survival, highlighting the positive impact of the molecule on liver health.

The study indicates that 1D-142 could be applied to other patients with severe liver conditions, such as acute-on-chronic liver failure syndrome (ACLF), which represents a breakthrough in the management of serious liver diseases.

“The validation of RAC1 as a therapeutic target and the application of this molecule in animal models represents an important step towards effective therapies for a disease with limited treatment options,” said Dr. Guillermo Mazzolini,senior researcher at CONICET, dean of the Faculty of Biomedical Sciences at Universidad Austral, and director of the laboratory.

“Furthermore, we have evidence that supports the therapeutic potential of 1D-142 in the context of acute-on-chronic liver failure (ACLF), a syndrome that affects patients with cirrhosis and is characterized by acute liver decompensation accompanied by one or more other organ failures,” he added. This condition is associated with high short-term mortality and has a considerably high incidence, given that approximately one-third of hospitalized patients with cirrhosis develop ACLF as a complication.

The research was conducted as part of the doctoral thesis of Barbara Bueloni, a fellow at IIMT, under the supervision of Drs. Guillermo Mazzolini and Juan Miguel Bayo Fina, in the Experimental Hepatology and Gene Therapy Laboratory. The study included the participation of Esteban Fiore, the contribution of the research team, and the collaboration of Dr. Julieta Comin (INTI), who was involved in the initial stages of the development of the evaluated molecule.

What was tested and what does it mean?

The treatment was tested in three different animal models of fulminant hepatitis and in ex vivo human liver tissue. In all cases, the results were consistent and significant:

In simple terms, this means that the treatment reduced the indicators of liver damage in the blood by almost half, which suggests that the treated livers suffered considerably less than those that did not receive the molecule.

Challenges and future of research

This discovery is part of an innovation strategy that unites efforts between academia and the biotechnology industry, using an international patent pending for its development. The joint work with the National Institute of Industrial Technology (INTI) has been fundamental in this process.

The development was developed within a research ecosystem that promotes the coordination of basic science, public institutions, and private sector actors. Within this framework, the biotechnology company Spectrum—linked to the laboratory and focused on innovative therapies for liver diseases—is participating as a strategic partner in the development of this technology, alongside the University and CONICET.

The technology already has an international patent (PCT) pending and is projected as a therapeutic platform for multiple forms of liver failure, including fulminant hepatitis and acute-on-chronic liver failure.