Benzinga | Nov 11, 2021 06:01PM EST

MediciNova Announces MN-001 Data Regarding Lipid Metabolism In NASH/NAFLD To Be Presented At The Liver Meeting 2021

MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), today announced that MediciNova's research collaborator Masatsune Ogura, M.D., Ph.D., Associate Professor at the Department of General Medical Science, Chiba University Graduate School of Medicine, is presenting results and findings of a study that investigated the mechanism by which MN-001 (tipelukast) alters triglyceride (TG) metabolism in hepatocytes at The Liver Meeting(r) 2021, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) to be held online from November 12th to 15th. In this study, HepG2 cells derived from human hepatocellular carcinoma samples were incubated for 48 hours with arachidonic acid (AA), LXR agonist T0901317, and MN-001 (tipelukast) each alone or in various combinations. The amount of TG synthesis in the HepG2 cells was calculated by extracting lipids from the HepG2 cells before and after treatment. As a result, it was found that MN-001 had an inhibitory effect on TG synthesis in HepG2 cells.



To further clarify part of the mechanism, mRNA was extracted from cell samples and the mRNA expression of molecules related to TG metabolism was measured using real-time PCR. As a result, the expression of CD36, one of the fatty acid transporters involved in the uptake of AA into liver cells, was suppressed in the samples by adding MN-001. This suggests that MN-001 reduces TG synthesis by inhibiting the AA uptake into hepatocytes. CD36 enhances cellular fatty acid uptake in the liver and is known to be involved in the pathogenesis of fatty liver.

The highlights of the presentation entitled "Improvement of Intracellular Lipid Metabolism by Tipelukast in the Pathogenesis of NASH/NAFLD" (Poster Publication # 1793) are as follows:

* TG synthesis (?g/mg protein) in HepG2 cells Compared to the vehicle, T0901317 alone increased TG synthesis by 3.8-fold, AA alone increased TG synthesis by 15.3-fold, and the combination of T0901317 + AA increased TG synthesis by 24.3-fold. Compared to MN-001 alone, the combination of T0901317 + MN-001 increased TG synthesis by 1.7-fold, the combination of AA + MN-001 increased TG synthesis by 3.7-fold, and the combination of T0901317 + AA + MN-001 increased TG synthesis by 3.7-fold.

* CD36 mRNA expression was downregulated in all 4 groups (vehicle, T0901317 alone, AA alone, T0901317 + AA) by adding MN-001.

* It was suggested that downregulation of CD36 expression is an important mechanism of MN-001. CD36 is one of the molecules responsible for fatty acid uptake into hepatocytes. MN-001 inhibits AA uptake into hepatocytes and suppresses TG synthesis, which is expected to reduce TG accumulation in hepatocytes.

Kazuko Matsuda, M.D. Ph.D, MPH., Chief Medical Officer, MediciNova, Inc., commented, "We are very pleased to present new results and findings from our collaboration with Dr. Ogura which elucidate MN-001's ability to improve lipid metabolism. In particular, its ability to suppress CD36 expression and reduce intracellular triglyceride synthesis may account for the role of MN-001 in NASH/NAFLD pathogenesis in addition to the significant lowering of serum triglyceride levels which was observed in multiple clinical trials."