New active against hepatic steatosis
There are currently no drugs for the targeted therapy of non-alcoholic fatty liver disease (NAFLD) or for the treatment of non-alcoholic fatty liver disease. fatty liver inflammation (NASH). But researchers are now reporting a new active substancethat is to fatty liver hepatitis proved to be very effective and well tolerated.
Mainz researchers have helped 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 inflammation and scarring of the liver. The research, published in the Journal of Hepatology, indicates a breakthrough in the treatment of this disease.
No established therapy to date
According to a current report from the University Medical Center of the Johannes Gutenberg University Mainz, more and more people in industrialized countries of the world are suffering from metabolic diseases such as obesity, impaired lipid metabolism or diabetes mellitus from kind 2.
Many of these patients develop fatty liver disease, known as non-alcoholic fatty liver disease (NAFL). In this country alone, about 30% of the population has NAFL. This is not a problem.
However, approximately one in six NAFL patients develop fatty liver disease, known as non-alcoholic steatohepatitis (NASH). So far, there are no established therapies and no approved drugs for non-alcoholic fatty liver disease.
Possible serious complications
When fatty liver disease becomes chronic, it leads to liver fibrosis. Collagen connective tissue in the liver increases and organ scars. Complications of fibrosis caused by NASH can be liver cirrhosis (shrunk liver), liver failure, and hepatocellular carcinoma.
Previous treatment for NAFL and NASH initially focused on changing the diet of those affected and prescribing more physical activity. This aims, among other things, to reduce weight. It can improve NASH.
As with the treatment of obesity, however, weight loss is often insufficient for most NASH patients. Drug therapy is currently not available.
Researchers are working on many active ingredients, but their approval has often failed due to insufficient efficacy or because they have caused undesirable side effects.
Entirely new class of substances
“In collaboration with Northsea Therapeutics, we have developed a potential NASH drug and tested it extensively in vitro and in vivo for its efficacy: structurally modified omega-3 fatty acid icosabutate. “, explains Univ.-Prof. doctor doctor Detlef Schuppan, director of the Institute for Translational Immunology at the University Medical Center Mainz.
“This is a whole new class of substances. Icosabutate improved both liver inflammation and liver fibrosis. In a first study with patients at high risk of NASH, one daily capsule of our active ingredient icosabutate very convincingly and quickly normalized high blood values of liver inflammation and fibrosis.says the researcher.
“Based on these promising results, a phase 2b clinical trial (“ICONA”) has been initiated in the United States in which patients with severe NASH and liver fibrosis are treated with icosabutate over a period of ‘a 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.
Main omega-3 fatty acids
According to the information, the development of the new drug is based on known substances from fish oil, 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, omega-3 fatty acids are quickly depleted by the body. Therefore, they no longer have sufficient potential to inhibit liver inflammation.
According to experts, the high doses of omega-3 fatty acids necessary for clinical efficacy are poorly tolerated and have undesirable side effects.
“With our substance icosabutate, we have changed the structure of the omega-3 fatty acid in such a way that this active substance cannot be incorporated into liver cells or used as ‘fuel’. There is enough unused fatty acid icosabutate in the liver to alleviate inflammation and fibrosis.”explains Professor Schuppan.
According to the expert, the modified omega-3 fatty acid icosabutate is 50 times stronger than natural omega-3 fatty acid. The researchers are optimistic that the active substance that has been developed will lead to the first effective therapy with clear benefits for many NASH sufferers. (ad)
Author and source information
This text corresponds to the requirements of the specialized medical literature, medical guidelines and current studies and has been verified by health professionals.
- University Medicine of the Johannes Gutenberg University Mainz: Researchers at the Medical University of Mainz develop an active ingredient against fatty liver disease, (accessed: 03.05.2022), University Medicine of the Johannes Gutenberg University Mainz
- Fraser DA, Wang X., Lund J., Nikolić N., Iruarrizaga-Lejaretta M., Skjaeret T., Alonso C., Kastelein JJP, Rustan AC, Kim YO, Schuppan D.: A structurally modified fatty acid, the icosabutate, suppresses liver inflammation and fibrosis in NASH; in: Journal of Hepatology, (published online: 2021-12-13 and in volume 76, number 4, P800-811: 2022-04-01), Journal of Hepatology
This article contains general advice only and should not be used for self-diagnosis or treatment. It cannot substitute a visit to the doctor.