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

64 Pages Posted: 31 Aug 2021 Publication Status: Review Complete

See all articles by Masayuki Aso

Masayuki Aso

CellGenTech, Inc.

Tokuo Yamamoto

CellGenTech, Inc.

Masayuki Kuroda

Chiba University - Center for Advanced Medicine

Jun Wada

Okayama University - Department of Nephrology, Rheumatology, Endocrinology and Metabolism

Yoshitaka Kubota

Chiba University - Department of Plastic and Reconstructive Surgery

Ko Ishikawa

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

Yoshiro Maezawa

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

Ayako Tawada

Chiba University - Department of Ophthalmology and Visual Science

Sakiyo Asada

CellGenTech, Inc.

Yasuyuki Aoyagi

CellGenTech, Inc.

Mika Kirinashizawa

CellGenTech, Inc.

Akinobu Onitake

CellGenTech, Inc.

Yuta Matsuura

CellGenTech, Inc.

Kunio Yasunaga

CellGenTech, Inc.

Shun-ichi Konno

CellGenTech, Inc.

Katsuaki Nishino

CellGenTech, Inc.

Misato Yamamoto

CellGenTech, Inc.

Junko Miyoshi

CellGenTech, Inc.

Norihiko Kobayashi

CellGenTech, Inc.

Masami Tanio

CellGenTech, Inc.

Takayuki Ikeuchi

Chiba University - Clinical Research Center

Hidetoshi Igari

Chiba University - Division of Infection Control

Nobuyuki Mitsukawa

Chiba University - Department of Plastic and Reconstructive Surgery

Hideki Hanaoka

Chiba University - Clinical Research Center

Koutaro Yokote

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

Yasushi Saito

Chiba University

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Multiple version iconThere are 2 versions of this paper

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

Suggested Citation

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.

Masayuki Aso

CellGenTech, Inc. ( email )

Chiba
Japan

Tokuo Yamamoto (Contact Author)

CellGenTech, Inc. ( email )

Chiba
Japan

Masayuki Kuroda

Chiba University - Center for Advanced Medicine ( email )

Chiba
Japan

Jun Wada

Okayama University - Department of Nephrology, Rheumatology, Endocrinology and Metabolism ( email )

Okayama
Japan

Yoshitaka Kubota

Chiba University - Department of Plastic and Reconstructive Surgery ( email )

Chiba
Japan

Ko Ishikawa

Chiba University - Department of Endocrinology, Hematology and Gerontology

Japan

Chiba University - Division of Diabetes, Metabolism and Endocrinology

1-8-1 Inohana
Chuo-ku, Chiba City
Chiba, 260-8677
Japan

Chiba University - Department of Clinical Cell Biology and Medicine

1-8-1 Inohana
Chuo-ku
Chiba City, Chiba 260-8670
Japan

Yoshiro Maezawa

Chiba University - Department of Endocrinology, Hematology and Gerontology

Japan

Chiba University - Division of Diabetes, Metabolism and Endocrinology

1-8-1 Inohana
Chuo-ku, Chiba City
Chiba, 260-8677
Japan

Chiba University - Department of Clinical Cell Biology and Medicine

1-8-1 Inohana
Chuo-ku
Chiba City, Chiba 260-8670
Japan

Ayako Tawada

Chiba University - Department of Ophthalmology and Visual Science ( email )

Chiba
Japan

Sakiyo Asada

CellGenTech, Inc. ( email )

Chiba
Japan

Yasuyuki Aoyagi

CellGenTech, Inc. ( email )

Chiba
Japan

Mika Kirinashizawa

CellGenTech, Inc. ( email )

Chiba
Japan

Akinobu Onitake

CellGenTech, Inc. ( email )

Chiba
Japan

Yuta Matsuura

CellGenTech, Inc. ( email )

Chiba
Japan

Kunio Yasunaga

CellGenTech, Inc. ( email )

Chiba
Japan

Shun-ichi Konno

CellGenTech, Inc. ( email )

Chiba
Japan

Katsuaki Nishino

CellGenTech, Inc. ( email )

Chiba
Japan

Misato Yamamoto

CellGenTech, Inc. ( email )

Chiba
Japan

Junko Miyoshi

CellGenTech, Inc. ( email )

Chiba
Japan

Norihiko Kobayashi

CellGenTech, Inc. ( email )

Chiba
Japan

Masami Tanio

CellGenTech, Inc. ( email )

Chiba
Japan

Takayuki Ikeuchi

Chiba University - Clinical Research Center ( email )

1-8-1 Inohana, Chuo-ku
Chiba City, 260-8677
Japan

Hidetoshi Igari

Chiba University - Division of Infection Control ( email )

Chiba
Japan

Nobuyuki Mitsukawa

Chiba University - Department of Plastic and Reconstructive Surgery ( email )

Chiba
Japan

Hideki Hanaoka

Chiba University - Clinical Research Center ( email )

1-8-1 Inohana, Chuo-ku
Chiba City, 260-8677
Japan

Koutaro Yokote

Chiba University - Department of Endocrinology, Hematology and Gerontology ( email )

Japan

Chiba University - Division of Diabetes, Metabolism and Endocrinology ( email )

1-8-1 Inohana
Chuo-ku, Chiba City
Chiba, 260-8677
Japan

Chiba University - Department of Clinical Cell Biology and Medicine ( email )

1-8-1 Inohana
Chuo-ku
Chiba City, Chiba 260-8670
Japan

Yasushi Saito

Chiba University ( email )

1-33, Yayoi-cho
Inage-ku
Chiba-shi, Chiba, 263-8, 271-8510
Japan

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