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Ann. Rheum. Dis., Jan 31 2025, S0003-4967(25)00070-6 | https://doi.org/10.1016/j.ard.2024.11.005
Mitochondrial transplantation as a novel therapeutic approach in idiopathic inflammatory myopathy
Jeong Yeon Kim 1, Young Cheol Kang 2, Min Jung Kim 3, Seon Uk Kim 1, Hae Rim Kang 1, Jeong Seon Yeo 2, Yujin Kim 2, Shin-Hye Yu 2, Byeongwook Song 2, Jung Wook Hwang 2, Yun-Sang Lee 4, Jung Woo Byun 4,5, Dae Hyun Yoo 6, Hyun Sook Kim 7, Kyuboem Han 2, Chun-Hyung Kim 2, Eun Young Lee 1
1Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
2Paean Biotechnology Inc, Seoul, Korea
3Division of Rheumatology, Department of Internal Medicine, Seoul Metropolitan Government–Seoul National University Hospital Boramae Medical Center, Seoul, Korea
4Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea
5Department of Biomedical Sciences, Seoul National University, Seoul, Korea
6Department of Rheumatology, College of Medicine, Hanyang University Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea
7Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
Correspondence to Dr Chun-Hyung Kim, Eun Young Lee
1Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
2Paean Biotechnology Inc, Seoul, Korea
3Division of Rheumatology, Department of Internal Medicine, Seoul Metropolitan Government–Seoul National University Hospital Boramae Medical Center, Seoul, Korea
4Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea
5Department of Biomedical Sciences, Seoul National University, Seoul, Korea
6Department of Rheumatology, College of Medicine, Hanyang University Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea
7Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
Correspondence to Dr Chun-Hyung Kim, Eun Young Lee
Abstract
Objectives: This study aimed to investigate the efficacy of mitochondrial transplantation as a therapeutic intervention for idiopathic inflammatory myopathy (IIM). This study used a comprehensive approach, incorporating both in vitro and in vivo IIM models, and conducted a first-in-human clinical trial to assess the effectiveness and safety of mitochondria isolated from human umbilical cord mesenchymal stem cells (PN-101).
Methods: Mitochondria isolated from umbilical cord mesenchymal stem cells were designated as PN-101. The efficacy of PN-101 was assessed using myoblasts derived from patients with IIM and C2C12 mouse perforin/granzyme B-treated myoblasts as an in vitro IIM model. PN-101's effect on IIM was examined using C protein-induced myositis (CIM) mice as an in vivo model. The efficacy and safety of PN-101 were evaluated in a phase 1/2a clinical trial involving 9 adult patients with refractory polymyositis or dermatomyositis.
Results: The myoblasts derived from patients with IIM exhibited defects in mitochondrial function and myogenesis. PN-101 transplantation enhances muscle differentiation and mitochondrial function in IIM myoblasts. PN-101 also enhanced intracellular adenosine triphosphate content, cell viability, and myogenesis in C2C12 perforin/granzyme B-treated myoblasts. In an in vivo model, PN-101 reduced myositis severity by exhibiting anti-inflammatory effects and restoring the CIM-induced metabolic shift. In a phase 1/2a prospective clinical trial involving adult patients with refractory IIM, PN-101 demonstrated no severe adverse drug reactions and showed at least minimal improvement in the International Myositis Assessment and Clinical Studies Group (IMACS)-Total Improvement Scores (TISs) compared with baseline.
Conclusions: PN-101 transplantation could serve as a novel treatment for IIM by enhancing mitochondrial repair and reducing inflammation in muscle tissues.
Methods: Mitochondria isolated from umbilical cord mesenchymal stem cells were designated as PN-101. The efficacy of PN-101 was assessed using myoblasts derived from patients with IIM and C2C12 mouse perforin/granzyme B-treated myoblasts as an in vitro IIM model. PN-101's effect on IIM was examined using C protein-induced myositis (CIM) mice as an in vivo model. The efficacy and safety of PN-101 were evaluated in a phase 1/2a clinical trial involving 9 adult patients with refractory polymyositis or dermatomyositis.
Results: The myoblasts derived from patients with IIM exhibited defects in mitochondrial function and myogenesis. PN-101 transplantation enhances muscle differentiation and mitochondrial function in IIM myoblasts. PN-101 also enhanced intracellular adenosine triphosphate content, cell viability, and myogenesis in C2C12 perforin/granzyme B-treated myoblasts. In an in vivo model, PN-101 reduced myositis severity by exhibiting anti-inflammatory effects and restoring the CIM-induced metabolic shift. In a phase 1/2a prospective clinical trial involving adult patients with refractory IIM, PN-101 demonstrated no severe adverse drug reactions and showed at least minimal improvement in the International Myositis Assessment and Clinical Studies Group (IMACS)-Total Improvement Scores (TISs) compared with baseline.
Conclusions: PN-101 transplantation could serve as a novel treatment for IIM by enhancing mitochondrial repair and reducing inflammation in muscle tissues.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-02-04)
- 국내 연구진
- 생명과학 > 세포생물학
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