A CIC bioGUNE team discovers a new strategy to treat alcohol-induced liver damage based on RNA therapeutics

The team led by Dr Malu Martínez Chantar, from CIC bioGUNE, has identified a new therapeutic target to treat alcohol-associated liver disease, based on the modulation of the magnesium transporter CNNM4.

The study, published in Hepatology and selected cover of this journal, proposes an innovative strategy with RNA interference to reduce cell damage and improve liver function.

This breakthrough offers new hope for one of the main causes of liver transplantation worldwide.

An international research team led by Dr. Malu Martínez-Chantar, head of the Liver Diseases Laboratory at CIC bioGUNE, member of BRTA, and researcher at CIBERehd, has identified a new therapeutic target that could revolutionise the treatment of alcohol-induced liver damage.

The study, of international scope, has been published in the prestigious journal Hepatology and selected as the cover of the journal. With Dr. Irene González Recio as first author, it highlights an innovative approach based on the magnesium transporter CNNM4, which plays a key role in the development of this disease.

Alcohol-related liver damage is one of the leading causes of liver disease-related mortality worldwide. In Europe, it accounts for up to 80% of severe cases of liver disease and is one of the main reasons for liver transplantation in Western countries.

Magnesium is an essential cation for liver function; however, its deficiency is common in patients with alcohol-induced liver damage and is associated with more aggressive disease progression. The research reveals that the magnesium transporter CNNM4 is directly involved in the cation imbalance observed in patients and experimental models.

The researchers demonstrated that overexpression of CNNM4 leads to magnesium imbalances that aggravate cell damage by affecting mitochondria and the system responsible for managing stress within liver cells. These alterations are key to understanding disease progression.

In addition, the study presents a pioneering approach using RNA molecules specifically designed to reduce CNNM4 activity in the liver. This technique, applied in experimental models, restored cell function, reduced liver damage and improved levels of SAMe, a compound essential for the repair of alcohol-damaged proteins.

‘Our finding opens a completely new avenue for the treatment of alcohol-induced liver damage, providing a specific strategy based on RNA technology targeting the liver,’ say Dr Martínez Chantar and Dr Gonzalez Recio.

Alcohol-induced liver damage spans several stages, from fat accumulation in the liver to severe alcoholic hepatitis, cirrhosis and even liver cancer. This discovery paves the way for new therapies that could significantly improve patients’ quality of life.