First-in-Human Autologous Implantation of Genetically Modified Adipocytes Expressing LCAT for the Treatment of Familial LCAT Deficiency

Familial lecithin: cholesterol acyltransferase (LCAT) deficiency (FLD) is a severe inherited disease without a cure. Genetically modified adipocyte (GMAC) secreting LCAT (LCAT-GMAC) was developed to treat FLD. First-in-human autologous implantation of LCAT-GMACs was performed, showing to be safe and effective. The LCAT-GMAC implantation increased serum LCAT activity by approximately 50% of the baseline and sustained over three years. The patient exhibited apparent hemolysis by visual inspection. We found the presence of hemoglobin/haptoglobin complex in the patient's serum. The hemoglobin-haptoglobin complex was almost disappeared seven days after the implantation. Upon implantation of LCAT-GMAC, the patient's proteinuria decreased temporarily to mild levels and then gradually increased to the baseline. At 48 weeks after implantation, proteinuria deteriorated with the development of mild hypertension. To treat hypertension, the patient received antihypertensives, leading to the normalization of blood pressure. With the reduction of blood pressure, the proteinuria rapidly decreased to mild proteinuria levels.