Breakthrough in the treatment with a new active substance – Heilpraxis

New active ingredient against fatty liver inflammation

There are currently no drugs for the targeted treatment of non-alcoholic fatty liver disease (NAFLD) or for the therapy of non-alcoholic fatty liver inflammation (NASH). But researchers are now reporting on one new active substancewho is at fatty liver hepatitis proved to be highly effective and well tolerated.

Researchers from Mainz have helped to develop a new type of drug that could be used to effectively treat non-alcoholic fatty liver inflammation: the modified omega-3 fatty acid icosabutate. The active substance prevented the inflammation and scarring of the liver. The in the journal “Journal of HepatologyThe published research indicates a breakthrough in the treatment of this condition.

No established therapy to date

According to a recent Message of the University Medical Center of the Johannes Gutenberg University of Mainz, more and more people in industrialized countries are suffering from metabolic diseases such as adiposity (obesity), disturbed lipid metabolism or type 2 diabetes mellitus.

Many of these patients develop fatty liver that is non-alcoholic fatty liver (NAFL). In this country alone, about 30 percent of the population has an NAFL. This does not cause any problems.

However, around one in six NAFL patients develops fatty liver inflammation, known as non-alcoholic steatohepatitis (NASH). So far there is no established therapy and no approved drug against non-alcoholic fatty liver inflammation.

Serious complications possible

When fatty liver inflammation becomes chronic, it leads to liver fibrosis. The collagenous connective tissue in the liver increases and the organ scars. Complications of fibrosis caused by NASH can be cirrhosis of the liver (shrunken liver), liver failure and hepatocellular carcinoma.

The previous treatment of NAFL and NASH is initially aimed at changing the diet of those affected and prescribing more physical activity. Among other things, this is intended to achieve weight reduction. This can improve the NASH.

As with the treatment of obesity, however, weight loss is often inadequate for most NASH patients. Drug therapy is currently not available.

Researchers are working on numerous active ingredients, but their approval often failed due to insufficient effectiveness or because they caused undesirable side effects.

Completely new substance class

“Together with the company Northsea Therapeutics, we have developed a potential drug against NASH and tested it extensively in vitro and in vivo with regard to its effectiveness: the structurally modified omega-3 fatty acid icosabutate”, explains Univ.-Prof. dr dr Detlef Schuppan, Director of the Institute for Translational Immunology at the University Medical Center Mainz.

“This is a completely new class of substances. Icosabutate improved both liver inflammation and liver fibrosis. In a first study with patients who were at high risk for NASH, a daily capsule of our active ingredient icosabutate very convincingly and quickly normalized elevated blood values ​​of liver inflammation and liver fibrosis.”says the researcher.

“Based on these promising results, a phase 2b clinical trial (‘ICONA’) was initiated in the USA, in which patients with severe NASH and liver fibrosis are treated with icosabutate over a period of one year. Here, the success of the therapy is assessed at the beginning and at the end by means of a liver biopsy.”according to the scientist.

Important omega-3 fatty acids

According to the information, the development of the new drug is based on known substances from fish oil, the omega-3 fatty acids. In addition to the positive effect on the cardiovascular system, these fatty acids are also involved in several processes that can regulate liver inflammation and fibrosis.

This served as a starting point for the search for a drug that could be used to treat chronic liver inflammation. The challenge of making an effective drug for NASH from omega-3 fatty acids is that omega-3 fatty acids are needed almost everywhere in the body for general energy metabolism.

The liver also uses these fatty acids to generate energy and build its cells. As a result, the omega-3 fatty acids are quickly used up by the body. Therefore, they no longer have sufficient potential to inhibit liver inflammation.

According to the experts, the high doses of omega-3 fatty acids required for clinical effectiveness are poorly tolerated and have undesirable side effects.

“With our substance icosabutate, we have modified the structure of the omega-3 fatty acid in such a way that this active substance cannot be incorporated into the liver cells or used up as ‘fuel’. So there is enough unused icosabutate fatty acid in the liver to dampen inflammation and fibrosis.”explains Professor Schuppan.

According to the expert, the modified omega-3 fatty acid icosabutate is 50 times stronger than the natural omega-3 fatty acid. The researchers are optimistic that the active ingredient that has now been developed will lead to the first effective therapy with clear benefits for the many NASH sufferers. (ad)