LCAT-GMAC Cell Therapy Improves Symptoms in Patient with Familial LCAT Deficiency


Following implantation with CellGenTech’s LCAT-GMAC, the patient’s serum LCAT activity increased by approximately 50% of baseline.

LCAT-GMAC (CellGenTech), an autologous cell therapy consisting of genetically modified adipocytes (GMAC) expressing lecithin–cholesterol acyltransferase (LCAT) intended to manage familial LCAT deficiency (FLD), demonstrated improvement of symptoms in a single patient with FLD treated in a first-in-human clinical study.1 Data from the study was presented at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California.

LCAT-GMAC consists of adipocytes derived from approximately 20 g of extracted cutaneous fat from the patient that were genetically modified via viral vectors to express LCAT, the enzyme that patients with FLD are deficient in. LCAT-GMAC was then implanted into the patient; first author Masayuki Aso, the president and CEO of CellGenTech Inc., and colleagues noted that the LCAT-GMAC's implantation is removable if necessary. The patient’s treatment took place at Chiba University in Chiba, Japan. LCAT deficiency is a rare genetic disorder with symptoms that include kidney damage, anemia, vision problems, and an increased risk of atherosclerosis and cardiovascular disease.2 The current standard of care focuses on management of symptoms.

Following implantation with LCAT-GMAC, the patient’s serum LCAT activity increased by approximately 50% of baseline.1 This increase was maintained through to 240 weeks following the implantation. Furthermore, at 2 weeks after the implantation of LCAT-GMAC, the patient’s hemolytic anemia improved according to immunoblot analysis of the patient’s serum proteins. The patient’s corneal opacity, another condition related to FLD, did not show a bettering or worsening of symptoms following implantation.

In terms of safety, it was noted that the patient developed mild hypertension approximately 48 weeks after the implantation. A substantial worsening of the patient’s proteinuria, which was present before implantation, was also observed around this time. Aso and colleagues speculated that the worsening proteinuria might be caused by progression of renal injury related to the mild hypertension. Although, around 96 weeks postimplantation, the patient’s proteinurea improved dramatically and dropped substantially below the preimplantation baseline. This improvement was sustained through to 240 weeks. An additional adverse event reported was pain, which the patient experienced at the time of fat tissue extraction and LCAT-GMAC implantation. It was noted that following both procedures, complete healing had occurred within 2 to 3 days.

“Single-dose LCAT-GMAC maintained LCAT activity in an FLD patient for 5 years, improving significant symptoms such as hemolytic anemia and proteinuria,” Aso and colleagues wrote.1 “CellGenTech plans to use this established methodology to develop GMAC therapeutics for rare diseases [including various inherited diseases and metabolic disorders.]”

CellGenTech, Inc. is developing LCAT-GMAC in a collaboration with DyDo Pharma.2 The therapy is currently being evaluated in a phase 1/2 clinical trial. In addition to LCAT-GMAC, CellGenTech also has several other GMAC-based therapies in the nonclinical research phase of development. These include HA-GMAC for the treatment of hemophilia A, HB-GMAC for the treatment of hemophilia B, GLA-GMAC for the treatment of Fabry disease, and NGRF-GMAC for the treatment of retinitis pigmentosa. GLA-GMAC is being developed in a collaboration with Kyorin Pharmaceutical and HA-GMAC's development is being supported by the Japan Agency for Medical Research and Development.

1. Aso M, Yamamoto TT, Kuroda M, et al. One-and-done gene and cell therapy for familial LCAT deficiency using LCAT gene transduced human adipocytes. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Poster #801.
2. Pipeline. CellGenTech, Inc. Website. Accessed May 17, 2023.
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