Title: Placenta-derived drug laennec and porcine improve hereditary hemochromatosis without phlebotomy and ameliorate neurological symptoms of wilson disease through the action of “hepcidin inducer”

Abstract

Human hepcidin made by hepatocytes controls extracellular iron by regulating its intestinal absorption, recycling by macrophages, and release from storage spaces. Recent studies indicate that hepcidin deficiency underlies most known forms of hereditary hemochromatosis (H.H). Case1 (H.H): 44years-old male patient who developed type2 diabetes mellitus(T2DM) had elevated serum ferritin (SF) level (10,191ng/ml). Liver biopsy revealed remarkable iron deposition in hepatocytes and relatively advanced fibrosis (F3). Chromosomal analysis confirmed the presence of transferrin receptor type 2(TfR2) mutations. Infusion with Laennec has been done for 84 months　as the substitute for the repeated phlebotomy. At the end of the treatment, the serum ferritin level was decreased to 428.4ng/ml (significantly lower than the started level). HbA1c also improved with the same or lower dose of insulin (8.86.8%). Plural liver biopsies revealed remarkable improvements in the grade of both iron deposition and fibrosis (F3F1) of the liver tissue. Case2(Wilson Disease):34years-old male patient who was diagnosed as Wilson Disease (W.D) when he was 10 years old. Impaired biliary excretion leads to accumulation of copper in the liver. This copper promotes the generation of free radicals and cell damage. With a histidine residue of hepcidin at position 3, this region also has the potential to bind bivalent metal ions such as copper. The high affinity of hepcidin for copper suggests that hepcidin could bind copper in vivo.Here we showed that infusion with Laennec which was elucidated to induce hepcidin enhanced the urinary excretion of copper and improved neurological signs of W.D remarkably. The discovery of hepcidin and its role in iron and copper metabolism could lead to novel therapies for H.H. and W.D. The placenta-derived Laennec (parenteral)and Porcine (oral) which act as the “hepcidin inducer” actually improved iron overload of H.H patient without utilizing sequential phlebotomy.　These drugs also could improve the neurological symptoms of W.D through the action of hepcidin inducer.

Biography

Yuki HAMADA Graduated from School of Medicine, Hokkaido University in 1975. From1975-1977 He was medical trainee at Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan followed by Lecturer, Gastroenterology and Hepatology Department, Hokkaido University in 1977-1989. Research Fellow, Faculty of Life Science (Prof.F.L.Bygrave), Australian National University in 1988-1989, 1991. Manager, Gastroenterology section, National Nishi-Sapporo hospital1989-1998 and at present President, HAMADA Clinic for Hepatology and Gastroenterology from1998. He is having membership of International Association for the Study of the Liver, membership of the Japan Society of Hepatology, Medical Specialist of the Japan Society of Hepatology, Board Certified Physician of the Japan Society of Internal Medicine, Medical Specialist of the Japanese Society of Gastroenterolog, Medical Specialist of Japan Gastroenterological Endoscopy Society, Medical Specialist of the Japan Geriatrics Society and Medical Specialist of the Japan Society of Ultrasonic and Medicine