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    Home > Active Ingredient News > Digestive System Information > Back to back two Science sub-journal papers, Li Hongliang's team solved the dilemma of fatty hepatitis treatment

    Back to back two Science sub-journal papers, Li Hongliang's team solved the dilemma of fatty hepatitis treatment

    • Last Update: 2022-01-01
    • Source: Internet
    • Author: User
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    Written | Source of Cui Xueqin | China Science News Non-alcoholic fatty liver disease is currently the most common liver disease.
    There are nearly 2 billion patients worldwide, and the incidence is increasing rapidly
    .

    According to statistics, the probability of patients with non-alcoholic steatohepatitis (hereinafter referred to as "steatohepatitis") developing cirrhosis within 10-15 years is as high as 15%-25%
    .

    Therefore, the clinical demand for steatohepatitis drugs is urgent, and its global market is expected to reach 35 billion U.
    S.
    dollars in 2030
    .

    Acetyl-Coenzyme A carboxylase (ACC) is currently the most potential therapeutic target for steatohepatitis.
    Its inhibitors can significantly improve liver fatification, inflammation and fibrosis.
    The previous ACC inhibitors can cause serious side effects of elevated blood lipids.
    , Which greatly hinders its clinical application
    .

    On December 16, 2021, the team of Professor Li Hongliang of Wuhan University published two cover papers in the journal Science Translational Medicine, a subsidiary of Science
    .

    This is also the first time that the journal has published back-to-back two articles from the same research team at the same time since its inception
    .

    This research breaks through the problem of side effects of targeted ACC, solves the dilemma of targeted ACC in the treatment of steatohepatitis, provides an important theoretical basis for the development of ACC inhibitors, and puts forward a practical and feasible approach for the treatment of steatohepatitis by targeted ACC.
    Direction
    .

    Professor Li Hongliang said: "It took us 10 years of continuous research to solve this major clinical problem of cardiovascular and metabolic diseases
    .

    " Li Hongliang's team has been committed to the research of major clinical problems such as fatty hepatitis
    .

    The study revealed the core mechanism of the occurrence and development of steatohepatitis, and found that 12-lipoxygenase (ALOX12) is a key promoter of the steatohepatitis process.
    ALOX12 can directly target ACC1 and specifically and precisely regulate the ACC1 lysosomal degradation pathway
    .

    Based on this discovery, Li Hongliang’s team has developed a new small molecule compound that can precisely target the ALOX12-ACC1 protein interaction, promote ACC1 protein degradation, significantly inhibit the development of steatohepatitis, and more importantly, does not cause side effects such as hyperlipidemia
    .

    Figure A.
    IMA-1 inhibits ALOX12 and ACC1 protein interaction structure diagram; Figure B.
    The effect of IMA-1 in the treatment of steatohepatitis (red staining area represents the degree of liver fibrosis) At present, the prevalence of non-alcoholic fatty liver in China has exceeded 30 %, it has become a major public health problem and a serious social medical burden
    .

    Fatty liver is also an important risk factor for many cardiovascular diseases, metabolic diseases, tumors, etc.
    Once non-alcoholic steatohepatitis develops, it will significantly increase the risk of liver diseases such as cirrhosis, liver cancer, and liver failure
    .

    In view of the huge prevalence of steatohepatitis, serious health hazards and strong clinical needs, global pharmaceutical companies such as Pfizer, Eli Lilly, Gilead, and Novo Nordisk have accelerated the development of new drugs in this field
    .

    Deciphering non-alcoholic fatty liver, a major clinical problem related to the health and life safety of billions of people, is by no means a day's work.
    In step-by-step exploration, scientists are slowly approaching the truth
    .

    In recent years, Li Hongliang’s team has carried out a series of studies focusing on ALOX12 and found that ALOX12 is the core driver of liver and heart ischemia-reperfusion injury, which significantly aggravates the degree of organ inflammation and damage; and has developed small molecule inhibitors in mice and pigs.
    The monkey model fully confirmed the safety and effectiveness of small molecule drugs targeting ALOX12 in the treatment of organ damage
    .

    Related research published in Nature Medicine and Cell Metabolism provides new therapeutic targets and strategies for improving the prognosis of organ ischemia-reperfusion injury
    .

    Link to the paper: https:// https:// open reprint, welcome to forward to the circle of friends and WeChat group 
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