Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain

Yeongduk An; Young Je Kim; Chung sei Kim; Hyeona Yim; Myungseob Kim; Eui Kyung Lee; Hyeon Ji Oh; Jun Hyeok Han; Eunseon Yoo; Sunghyun Kim; Joongseok Woo; Edward R.B. Moore; Ji Youn Jung; Wooram Park

doi:10.1007/s00253-021-11640-0

Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain

Yeongduk An, Young Je Kim, Chung sei Kim, Hyeona Yim, Myungseob Kim, Eui Kyung Lee, Hyeon Ji Oh, Jun Hyeok Han, Eunseon Yoo, Sunghyun Kim, Joongseok Woo, Edward R.B. Moore, Ji Youn Jung, Wooram Park

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	8727-8737
Number of pages	11
Journal	Applied Microbiology and Biotechnology
Volume	105
Issue number	23
DOIs	https://doi.org/10.1007/s00253-021-11640-0
State	Published - Dec 2021

Keywords

ATCC19397
Botulinum neurotoxin type A
CCUG7968
Compound muscle action potential
Dystrophin
Muscle contraction
Neural cell adhesion molecule
Neuromuscular junction

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10.1007/s00253-021-11640-0

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@article{b2ede04cfb584577b632aa2258e851f6,

title = "Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain",

abstract = "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 \textasciitilde{} 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{\textregistered} (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.",

keywords = "ATCC19397, Botulinum neurotoxin type A, CCUG7968, Compound muscle action potential, Dystrophin, Muscle contraction, Neural cell adhesion molecule, Neuromuscular junction",

author = "Yeongduk An and Kim, \{Young Je\} and Kim, \{Chung sei\} and Hyeona Yim and Myungseob Kim and Lee, \{Eui Kyung\} and Oh, \{Hyeon Ji\} and Han, \{Jun Hyeok\} and Eunseon Yoo and Sunghyun Kim and Joongseok Woo and Moore, \{Edward R.B.\} and Jung, \{Ji Youn\} and Wooram Park",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2021",

month = dec,

doi = "10.1007/s00253-021-11640-0",

language = "English",

volume = "105",

pages = "8727--8737",

journal = "Applied Microbiology and Biotechnology",

issn = "0175-7598",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "23",

}

TY - JOUR

T1 - Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain

AU - An, Yeongduk

AU - Kim, Young Je

AU - Kim, Chung sei

AU - Yim, Hyeona

AU - Kim, Myungseob

AU - Lee, Eui Kyung

AU - Oh, Hyeon Ji

AU - Han, Jun Hyeok

AU - Yoo, Eunseon

AU - Kim, Sunghyun

AU - Woo, Joongseok

AU - Moore, Edward R.B.

AU - Jung, Ji Youn

AU - Park, Wooram

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

KW - ATCC19397

KW - Botulinum neurotoxin type A

KW - CCUG7968

KW - Compound muscle action potential

KW - Dystrophin

KW - Muscle contraction

KW - Neural cell adhesion molecule

KW - Neuromuscular junction

UR - https://www.scopus.com/pages/publications/85118254324

U2 - 10.1007/s00253-021-11640-0

DO - 10.1007/s00253-021-11640-0

M3 - Article

C2 - 34716460

AN - SCOPUS:85118254324

SN - 0175-7598

VL - 105

SP - 8727

EP - 8737

JO - Applied Microbiology and Biotechnology

JF - Applied Microbiology and Biotechnology

IS - 23

ER -

Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain

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Keywords

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