On February 15, the National Key Laboratory of Major Disease New Drug Target Development and New Drug Creation of GMU published its latest research findings online in the international authoritative journal Science•Translational Medicine (Impact Factor 17.1), titled "Multispecies Translatomics Identities SIKE as a MAPK Reporter That Prevents NASH Progress", expositing that "SIKE" is a new key therapeutic target for Nonalcoholic Fatty Liver Disease (NAFLD). The corresponding authors of this academic paper are Professor Li Hongliang from the Gannan Institute of Innovation and Translational Medicine of GMU, as well as Professor Zhang Xiaojing, Huang Lingli, Bai Lan, Cheng Xu, Yang Hailong, etc.
NAFLD is the most common chronic liver disease at present, affecting more than a quarter of the global population, and the incidence rate is still rising rapidly. The spectrum of NAFLD diseases includes simple Nonalcoholic Fatty Liver (NAFL), Non-alcoholic Steatohepatitis (NASH), and liver fibrosis. About 25% of NAFL patients will progress to NASH, greatly increasing the risk of end-stage liver diseases such as cirrhosis, liver cancer, and liver failure. It is also a high-risk factor for cardiovascular and cerebrovascular diseases and malignant tumors.
Given the large number of cases, serious health risks, and strong clinical demand of NASH, there have been over 1,400 clinical trials worldwide targeting NASH, but no specific therapeutic drugs have been approved yet. A deep understanding of the core factors that contribute to the progression of NAFL towards NASH, the search for therapeutic targets, and the development of effective drugs are key to the treatment of NASH.
The study systematically conducted multi-species omics analysis, combined with functional and mechanistic studies, and discovered IKKε the suppressor (SIKE) is a key target of NASH, which can effectively inhibit the transition of NAFL to NASH. SIKE directly targets TGF-β-Activated Kinase 1 (TAK1) and blocks MAPK signal to exert anti-NASH effects.
More importantly, through high-throughput screening, this study found that indoprofen (a safe and effective anti-platelet drug) significantly enhanced the expression of SIKE, effectively improving the progression of NASH in mice and cynomolgus monkeys, without any significant toxic side effects. This study proposes a new concept and direction of targeted SIKE therapy for NASH, develops new functions and mechanisms of indobufen therapy for NASH, and provides new clinical optional strategies and drugs for NASH treatment.
The journal Science•Translational Medicine is an important sub-issue of the internationally renowned journal Science, and it is oriented to disseminating major discoveries and breakthroughs in the fields of biomedical, translational, and clinical sciences worldwide. It publishes the latest research results that can fill the gap between basic research and medical applications, promoting human health.
The National Key Laboratory of Major Disease New Drug Target Development and New Drug Creation of GMU focuses on solving major scientific and technological problems such as insufficient original innovation capacity, low competitiveness of high value-added products, and disconnection of the innovation chain and industrial chain in China's new drug creation. It conducts forward-looking, strategic, and systematic basic application transformation research and key core technology breakthroughs. It has published more than 1,000 high-level research papers in the international authoritative journals such as Science, Nature, Nat Med, Nat Commun, Cell Metab, Sci Transl Med, providing important theoretical basis and clinical treatment strategies for the prevention and treatment of major diseases with high incidence.
