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Sporadic Inclusion Body Myositis Underling Mitochondrial Dysfunction Ameliorated by Mitochondrial Homing Drug, MA-5

55 Pages Posted: 14 Nov 2019

See all articles by Yoshitsugu Oikawa

Yoshitsugu Oikawa

Tohoku University

Rumiko Izumi

Tohoku University - Graduate School of Medicine

Masashi Koide

Tohoku University

Yoshihiro Hagiwara

Tohoku University

Makoto Kanzaki

Tohoku University

Naoki Suzuki

Tohoku University - Graduate School of Medicine

Koichi Kikuchi

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Tetsuro Matsuhashi

Tohoku University

Yukako Akiyama

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Mariko Ichijo

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Takafumi Toyohara

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Takehiro Suzuki

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Eikan Mishima

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Yoshiaki Ogata

Tohoku University

Yasutoshi Akiyama

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Chitose Suzuki

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Masashi Aoki

Tohoku University Hospital - Department of Neurology

Eiji Itoi

Tohoku University

Shigeo Kure

Tohoku University

Ken-ichiro Hayashi

Okayama University of Sciences

Takaaki Abe

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

More...

Abstract

Background: Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and mitochondrial abnormalities may be involved.

Methods: We recruited 9 sIBM patients and we examined mitochondrial functions with bioenergetic and examinations and dynamics of patient myoblasts with measuring a mitochondrial disease marker growth differential factor 15 (GDF15). We also examined the effect of a new candidate drug, Mitochondria acid-5 (MA-5).

Findings: Bioenergetic analysis of sIBM patient myoblasts revealed damaged mitochondrial function with decreased ATP, mitochondrial size and impaired mitochondrial dynamics and cell vulnerability. MA-5 increased the ATP level and reduced mitochondrial ROS, following the protection against cell death. The reduced levels of Opa1 and Drp1 showed the impairment of mitochondrial fusion/fission process and that MA-5 ameliorated. Skin fibroblasts from sIBM patients can be used for diagnosis.

Interpretation: GDF15 and MA-5 could provide both a new maker and therapeutic strategy for sIBM patients.

Funding Statement: These works were supported in part by National grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18H02822), Translational Research Network Program (C50) from Japan Agency for Medical Research and Development (AMED). MEXT and AMED, JAPAN.

Declaration of Interests: The authors state: "None."

Ethics Approval Statement: Myoblasts and fibroblasts obtained by muscle and skin biopsy of sIBM patients were collected in Tohoku University Hospital under the approval of the Ethical Committee of Tohoku University.

Keywords: Sporadic inclusion body myositis (sIBM), mitochondrial dysfunction, GDF15, fusion/fission, mitochondrial dynamics, mitochonic acid-5 (MA-5)

Suggested Citation

Oikawa, Yoshitsugu and Izumi, Rumiko and Koide, Masashi and Hagiwara, Yoshihiro and Kanzaki, Makoto and Suzuki, Naoki and Kikuchi, Koichi and Matsuhashi, Tetsuro and Akiyama, Yukako and Ichijo, Mariko and Toyohara, Takafumi and Suzuki, Takehiro and Mishima, Eikan and Ogata, Yoshiaki and Akiyama, Yasutoshi and Suzuki, Chitose and Aoki, Masashi and Itoi, Eiji and Kure, Shigeo and Hayashi, Ken-ichiro and Abe, Takaaki, Sporadic Inclusion Body Myositis Underling Mitochondrial Dysfunction Ameliorated by Mitochondrial Homing Drug, MA-5 (10/22/2019 04:46:20). Available at SSRN: https://ssrn.com/abstract=3474487 or http://dx.doi.org/10.2139/ssrn.3474487

Yoshitsugu Oikawa

Tohoku University

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Rumiko Izumi

Tohoku University - Graduate School of Medicine

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Masashi Koide

Tohoku University

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Yoshihiro Hagiwara

Tohoku University

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Makoto Kanzaki

Tohoku University

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Naoki Suzuki

Tohoku University - Graduate School of Medicine

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Koichi Kikuchi

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Sendai
Japan

Tetsuro Matsuhashi

Tohoku University

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Yukako Akiyama

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Sendai
Japan

Mariko Ichijo

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Sendai
Japan

Takafumi Toyohara

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Sendai
Japan

Takehiro Suzuki

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Sendai
Japan

Eikan Mishima

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Sendai
Japan

Yoshiaki Ogata

Tohoku University

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Yasutoshi Akiyama

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Sendai
Japan

Chitose Suzuki

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine

Sendai
Japan

Masashi Aoki

Tohoku University Hospital - Department of Neurology ( email )

1-1 Seiryo-machi
Sendai, 980-8574
Japan

Eiji Itoi

Tohoku University

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Shigeo Kure

Tohoku University

SKK Building, Katahira 2
Aoba-ku, Sendai, Miyagi 980-8577
Japan

Ken-ichiro Hayashi

Okayama University of Sciences

Okayama
Japan

Takaaki Abe (Contact Author)

Tohoku University - Division of Nephrology, Endocrinology and Vascular Medicine ( email )

Sendai
Japan