Chiba University - Department of Endocrinology, Hematology and Gerontology; Chiba University - Division of Diabetes, Metabolism and Endocrinology; Chiba University - Department of Clinical Cell Biology and Medicine
Chiba University - Department of Endocrinology, Hematology and Gerontology; Chiba University - Division of Diabetes, Metabolism and Endocrinology; Chiba University - Department of Clinical Cell Biology and Medicine
Chiba University - Department of Endocrinology, Hematology and Gerontology; Chiba University - Division of Diabetes, Metabolism and Endocrinology; Chiba University - Department of Clinical Cell Biology and Medicine
First-in-Human Autologous Implantation of Genetically Modified Adipocytes Expressing LCAT for the Treatment of Familial LCAT Deficiency
Number of pages: 64Posted: 31 Aug 2021
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Abstract
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.
Keywords: cholesterol homeostasis, ex vivo genetherapy, familial LCAT deficiency, genetic disease, hemolytic anemia, HDL, LCAT, proteinuria, plasma lipoprotein, renal injury
Aso, Masayuki and Yamamoto, Tokuo and Kuroda, Masayuki and Wada, Jun and Kubota, Yoshitaka and Ishikawa, Ko and Ishikawa, Ko and Maezawa, Yoshiro and Maezawa, Yoshiro and Tawada, Ayako and Asada, Sakiyo and Aoyagi, Yasuyuki and Kirinashizawa, Mika and Onitake, Akinobu and Matsuura, Yuta and Yasunaga, Kunio and Konno, Shun-ichi and Nishino, Katsuaki and Yamamoto, Misato and Miyoshi, Junko and Kobayashi, Norihiko and Tanio, Masami and Ikeuchi, Takayuki and Igari, Hidetoshi and Mitsukawa, Nobuyuki and Hanaoka, Hideki and Yokote, Koutaro and Saito, Yasushi, First-in-Human Autologous Implantation of Genetically Modified Adipocytes Expressing LCAT for the Treatment of Familial LCAT Deficiency. Available at SSRN: https://ssrn.com/abstract=3915012 or http://dx.doi.org/10.2139/ssrn.3915012
This version of the paper has not been formally peer reviewed.
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