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Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain

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Abstract

Botulinum neurotoxin type A (BoNT/A) induces muscle atrophy by cleaving synaptosomal-associated protein 25. Thus, BoNT/A has been actively utilized for the treatment of masseter and gastrocnemius hypertrophy. In this study, INI101 toxin was newly identified from the CCUG 7968 strain, and its therapeutic efficacy was evaluated both in vitro and in vivo. The INI101 toxin showed identical genetic sequence, amino acid sequence, and protein subunit composition to BoNT/A produced from strain Hall A. Electromyography (EMG), and immunofluorescence staining demonstrated that INI101 (at 2 ~ 8 U/rat) effectively blocked the neuromuscular junction with no toxicity in a rat model. The EMG results showed INI101 toxin–induced weight loss and volume reduction of the gastrocnemius, similar to the effects of Botox® (BTX). Histological and immunofluorescence staining was consistent with this EMG result, showing that INI101 toxin caused muscle fiber reduction in the gastrocnemius. Notably, INI101 toxin diffused less into adjacent muscle tissue than BTX, indicating that INI101 toxin may reduce potential side effects due to diffusion into normal tissues. INI101 toxin isolated from the novel strain CCUG 7968 is a newly identified meaningful biopharmaceutical comparable to the conventional BoNT/A in the medical field.

Key points

• Botulinum neurotoxin type A (BoNT/A, INI101) was identified from the CCUG 7968 strain.

• INI101 toxin showed similar safety and therapeutic efficacy comparable to conventional BoNT/A both in vitro and in vivo.

• INI101 toxin is a meaningful biopharmaceutical comparable to the conventional BoNT/A in the medical field.

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Data availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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Funding

This work was funded by INIBIO Co., Ltd., grant number (Bucheon, Korea; INI101), Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant no. NRF 2021R1A2C1010912), and the Catholic University of Korea, Research Fund, 2020.

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Author notes

  1. Yeongduk An and Young-Je Kim These authors contributed equally to work

Authors and Affiliations

  1. Department of Companion & Laboratory Animal Science, Experimental and Toxicologic Pathology, Kongju National University, 56 Gongju Daehak-ro, Chungnam, 32588, Republic of Korea

    Yeongduk An, Eunseon Yoo, Sunghyun Kim, Joongseok Woo & Ji-Youn Jung

  2. Research & Development Center, INIBIO Co., Ltd., Bucheon, Gyeonggi, 14445, Republic of Korea

    Young-Je Kim, Chung-sei Kim & Hyeona Yim

  3. School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea

    Myungseob Kim & Eui-Kyung Lee

  4. Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi, 14662, Republic of Korea

    Hyeon-Ji Oh, Jun-Hyeok Han & Wooram Park

  5. Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi, 14662, Republic of Korea

    Hyeon-Ji Oh, Jun-Hyeok Han & Wooram Park

  6. Culture Collection University of Gothenburg (CCUG), Sahlgrenska Academy of the University of Gothenburg, 41346, Gothenburg, Sweden

    Edward R. B. Moore

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  1. Yeongduk An
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Contributions

Y-JK, C-sK, HY, J-YJ, and WP conceived and designed research. YA, Y-JK, EY, SK, and JW conducted experiments. HY, C-sK, MK, E-KL, and ERBM contributed new reagents or analytical tools. HY, H.-JO, and J-HH analyzed data. Y-JK, J-YJ, and WP wrote the manuscript. All authors read and approved the manuscript.

Corresponding authors

Correspondence to Ji-Youn Jung or Wooram Park.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed as documented in the “Material and methods”.

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An, Y., Kim, YJ., Kim, Cs. et al. Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain. Appl Microbiol Biotechnol 105, 8727–8737 (2021). https://doi.org/10.1007/s00253-021-11640-0

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