"Why Treatment Was Ineffective" ... UNIST Identifies Inhibitory Substance for Non-Alcoholic Fatty Liver Disease Treatment

Professor Choi Jang-hyun and Professor Nam Deok-woo's Team Identifies Genetic Material That Reduces Drug Efficacy

A joint research team of Professors Janghyun Choi and Deokwoo Nam from the Department of Life Sciences at Ulsan National Institute of Science and Technology (UNIST) has identified an inhibitory substance for the treatment of non-alcoholic fatty liver disease. (From left: Professor Janghyun Choi, Researcher Hyunjun Jang, Researcher Yohan Lee, Professor Deokwoo Nam, Researcher Sungoo Kim)

[Asia Economy Yeongnam Reporting Headquarters Reporter Lee Seryeong] The reason why the efficacy of candidate drugs for non-alcoholic fatty liver disease (NAFLD) treatment has been unsatisfactory in clinical trials has been uncovered.

A joint research team led by Professors Choi Janghyun and Nam Deokwoo from the Department of Life Sciences at Ulsan National Institute of Science and Technology (UNIST) discovered that a genetic material in the liver called ‘MIR 20B’ suppresses the synthesis of proteins that help break down fat.

The research team explained that existing candidate drugs aimed to activate this protein to prevent fat accumulation in the liver, but MIR 20B interfered with the protein synthesis (expression) itself, reducing the drugs’ effectiveness.

MIR 20B is a type of microRNA, a non-coding RNA that, unlike RNA used in vaccines, does not contain protein-coding information.

It plays an important role in regulating the expression of genes that contain protein information, affecting the entire process by which various proteins are formed from genes.

The research team confirmed through animal experiments that administering an inhibitor of this genetic material improved the efficacy of the candidate drugs.

Non-alcoholic fatty liver disease is a broad condition in which excessive triglycerides accumulate in the liver, causing inflammation or leading to scar tissue formation and fibrosis due to inflammation.

If scar tissue continues to accumulate in the liver, it can progress to cirrhosis. Since no effective treatment has been developed yet, clinical research for drug development is ongoing.

Attempts to use fibrate-class drugs, which are used to treat hyperlipidemia, as treatments for NAFLD have been numerous, but they failed to pass clinical stages due to lack of histological effects such as improvement in liver fibrosis.

Fibrate-class drugs work by increasing the activity of the peroxisome proliferator-activated receptor alpha (PPARA) protein, which promotes fat breakdown.

Figure showing the pathogenesis of non-alcoholic fatty liver disease and the effect of administering MIR20B inhibitors.

The research team confirmed through animal experiments that MIR 20B, an RNA that suppresses the expression of a specific protein, inhibits the expression of the PPARA protein and reduces the efficacy of fenofibrate, a commercially available fibrate-class drug.

They first analyzed patients’ livers to identify the correlation between MIR 20B and the PPARA genome and validated it through animal experiments.

They also elucidated the specific process by which MIR 20B acts on the 3' untranslated region (3' UTR) of the mRNA copy containing the PPARA protein information, inhibiting PPARA protein synthesis.

When an MIR 20B inhibitor was administered together with fenofibrate to fatty liver model animals, it showed excellent effects in improving liver fibrosis.

This research was conducted with support from the National Research Foundation of Korea, the Korea Mouse Phenotyping Consortium (KMPC), and the UNIST Future Leading Project, and the results were published online on December 30 last year in the prestigious life sciences journal ‘eLife.’

Professor Choi Janghyun, who led the research, is the corresponding author of this paper along with Professor Nam Deokwoo. Researchers Lee Yohan, Dr. Jang Hyunjun, and Researcher Kim Sungoo participated as co-first authors.

Professor Choi Janghyun said, “There are limitations in developing NAFLD treatments using a single drug, so research on combination therapies has been actively conducted recently. Prescribing an MIR 20B inhibitor together with existing treatments could be an effective therapeutic approach for NAFLD.”

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