Research
Faculty Members
［Areas of cooperation］Cell Biology
Hirano Ken-ichiSpecially Appointed Professor
Mission: To overcome TGCV one day sooner
I discovered a novel cardiovascular disease named “Triglyceride deposit cardiomyovasculopathy (TGCV) (N Engl J Med. 2008). In this department, I am developing a first-in-class orphan drug, CNT-01, for patients with TGCV.
Favorite phrase: No short cut in science.
Research theme
Development of first-in-class orphan drug, CNT-01, for TGCV
TGCV is an emerging cardiovascular disease, in which defective intracellular lipolysis of long-chain triglyceride (TG) results in severe heart failure and diffuse coronary atherosclerosis with TG deposition. We are trying to develop a first-in-class orphan drug, CNT-01, of which major ingredient is tricaprin (C10:0TG). CNT-01 is designated as SAGIGAKE designation by the Ministry of Health, Labour, and Welfare of Japan.
Elucidation of molecular basis and pathophysiology of TGCV
TGCV is classified into primary and idiopathic types with and without genetic deficiency of adipose triglyceride lipase. As the principal investigator for Japan TGCV study group, we developed the diagnostic criteria for both TGCV subtypes, which has been published in the the guideline from the Japanese Circulation Society.
Elucidation for mechanism of action of CNT-01
Tricaprin is a prodrug. The active form is capric acid (C10:0). C10:0 alters the chemical composition of intracellular TG as well as enzyme(s) involved in the lipolytic action. As results, C10:0 reduces pre-deposited intracellular TGs and supplies long chain fatty acid for mitochondrial β-oxidation.
Application of CNT-01 to other cardiovascular diseases
Abdominal aortic aneurysm (AAA) is fatal when it ruptures. After obtaining pre-clinical proof of concept that C10:0TG regressed AAA in a rat model, we have finished the first-in-human AAA trial with tricaprin (F-HAAAT).
Representative achievements
Hirano K, Okamura S, Sugimura K, Miyauchi H, Nakano Y, Nochioka K, Hashimoto C, Iwanaga Y, Nakajima K, Yamaguchi S, Yasui Y, Shimamoto S, Hirano M, Okune M, Nishimura Y, Shimoyama H, Nagasawa Y, Amano T, Kuniyoshi S, Hui SP, Zaima N, Ikeda Y, Yamada T, Fujimoto S, Sakata Y, Kunishisa K, the Japan TGCV study group. Long-term survival and durable recovery of heart failure in patients with triglyceride deposit cardiomyovasculopathy. Nat Cardiovasc Res, 2025; 4: 266-274.
Hirano K, Miyauchi H, Nakano Y, Kawaguchi Y, Okamura S, Nishimura Y, Onishi T, Fujimoto S, Yamada T, Amano T. Overall survival rate of patients with triglyceride deposit cardiomyovasculopathy. JACC:Advances 2023;2(4):100347.
Hirano K, Higashi M, Nakajima K. Remarkable regression of diffuse coronary atherosclerosis in patients with triglyceride deposit cardiomyovasculopathy. Eur Heart J 2023;44(13):1191.
Hirano K, Ikeda Y, Sugimura K, Sakata Y. Cardiomyocyte steatosis and defective washout of iodine-123-beta-methyl iodophenyl-pentadecanoic acid in genetic deficiency of adipose triglyceride lipase. Eur Heart J 2015;36:580.
Ikeda Y, Hirano K*, Fukushima N, Sawa Y. A novel type of human spontaneous coronary atherosclerosis with triglyceride deposition. Eur Heart J 2014;35:875. *corresponding author
Hirano K, Ikeda Y, Zaima N, Sakata Y, Matsumiya G. Triglyceride deposit cardiomyovasculopathy. N Engl J Med 2008;359:2396-2398.
Miyaoka K, Kuwasako T, Hirano K*, Nozaki S, Yamashita S, Matsuzawa Y. CD36 deficiency associated with insulin resistance. Lancet 2001;357:686-687. *corresponding author
Hirano K, Yamashita S, Nakagawa Y, Ohya T, Matsuura F, Tsukamoto K, Okamoto Y, Matsuyama A, Matsumoto K, Miyagawa J, Matsuzawa Y. Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions. Circ Res 1999;85:108-116.
Hirano K, Young SG, Farese RV, Jr., Ng J, Sande E, Warburton C, Powell-Braxton LM, Davidson NO. Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48. J Biol Chem 1996;271:9887-9890.
Hirano K, Matsuzawa Y, Sakai N, Hiraoka H, Nozaki S, Funahashi T, Yamashita S, Kubo M, Tarui S. Polydisperse low-density lipoproteins in hyperalphalipoproteinemic chronic alcohol drinkers in association with marked reduction of cholesteryl ester transfer protein activity. Metabolism 1992;41:1313-1318.
