Abstract 50: A Phase I Clinical Trial Evaluating the Safety of With Allogeneic Adipose Tissue-derived Multilineage Progenitor Cells-transplantation Therapy in Homozygous Familial Hypercholesterolemia Patients

Abstract

Familial hypercholesterolemia (FH) is an inherited disorder, mainly caused by defects in low-density lipoprotein (LDL) receptor gene. The patients are characterized by high LDL cholesterol levels in the blood and premature cardiovascular disease. Although most of heterozygous FH patients are usually treated with statin, ezetimibe and bile acid sequestrants, homozygous FH patients are resistant to drug therapy. Therefore, in Japan, many of homozygous FH patients are treated by LDL-apheresis. LDL-apheresis is a great procedure to remove LDL cholesterol from the blood and contribute to improve prognosis of homozygous FH patients. However, the effect of removing LDL cholesterol is temporary and still not enough. As a definitive therapy, liver transplantation therapy could be one of options to recover LDL receptor, but donor is limited in Japan. Therefore, based on the increase of the evidence about the safety of mesenchymal stem cells and percutaneous transhepatic portal approach in islet transplantation, we have developed a cell transplantation therapy with allogeneic adipose tissue-derived multilineage progenitor cells (ADMPCs), as an alternative treatment instead of liver transplantation. Our group has already proved that xenogenic transplantation of human ADMPCs into Watanabe heritable hyperlipidemic rabbits resulted in significant reductions in total cholesterol, and the reductions were observed within 4 weeks and maintained for 12 weeks. These results suggested that hADMPC transplantation could correct the metabolic defects and be a novel therapy for inherited liver diseases. Here, we report a protocol for the first-in-human clinical trial, which has been approved by the institutional review board and Ministry of Health, Labour and Welfare, Japan.