Recombinant botulinum neurotoxin serotype A1 in vivo characterization

Abstract Clinically used botulinum neurotoxins (BoNTs) are natural products of Clostridium botulinum. A novel, recombinant BoNT type A1 (rBoNT/A1; IPN10260) has been synthesized using the native amino acid sequence expressed in Escherichia coli and has previously been characterized in vitro and ex v...

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Autores principales:	Cindy Périer, Vincent Martin, Sylvie Cornet, Christine Favre‐Guilmard, Marie‐Noelle Rocher, Julien Bindler, Stéphanie Wagner, Emile Andriambeloson, Brian B. Rudkin, Rudy Marty, Alban Vignaud, Matthew Beard, Stephane Lezmi, Mikhail Kalinichev
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	botulinum muscle neurotoxin recombinant rodent SNAP25 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/08d7dae9cde34694bf838b65c8d1a5b6
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spelling	oai:doaj.org-article:08d7dae9cde34694bf838b65c8d1a5b62021-11-16T13:45:55ZRecombinant botulinum neurotoxin serotype A1 in vivo characterization2052-170710.1002/prp2.857https://doaj.org/article/08d7dae9cde34694bf838b65c8d1a5b62021-10-01T00:00:00Zhttps://doi.org/10.1002/prp2.857https://doaj.org/toc/2052-1707Abstract Clinically used botulinum neurotoxins (BoNTs) are natural products of Clostridium botulinum. A novel, recombinant BoNT type A1 (rBoNT/A1; IPN10260) has been synthesized using the native amino acid sequence expressed in Escherichia coli and has previously been characterized in vitro and ex vivo. Here, we aimed to characterize rBoNT/A1 in vivo and evaluate its effects on skeletal muscle. The properties of rBoNT/A1 following single, intramuscular administration were evaluated in the mouse and rat digit abduction score (DAS) assays and compared with those of natural BoNT/A1 (nBoNT/A1). rBoNT/A1‐injected tibialis anterior was assessed in the in situ muscle force test in rats. rBoNT/A1‐injected gastrocnemius lateralis (GL) muscle was assessed in the compound muscle action potential (CMAP) test in rats. The rBoNT/A1‐injected GL muscle was evaluated for muscle weight, volume, myofiber composition and immunohistochemical detection of cleaved SNAP25 (c‐SNAP25). Results showed that rBoNT/A1 and nBoNT/A1 were equipotent and had similar onset and duration of action in both mouse and rat DAS assays. rBoNT/A1 caused a dose‐dependent inhibition of muscle force and a rapid long‐lasting reduction in CMAP amplitude that lasted for at least 30 days. Dose‐dependent reductions in GL weight and volume and increases in myofiber atrophy were accompanied by immunohistochemical detection of c‐SNAP25. Overall, rBoNT/A1 and nBoNT/A1 exhibited similar properties following intramuscular administration. rBoNT/A1 inhibited motoneurons neurotransmitter release, which was robust, long‐lasting, and accompanied by cleavage of SNAP25. rBoNT/A1 is a useful tool molecule for comparison with current natural and future modified recombinant neurotoxins products.Cindy PérierVincent MartinSylvie CornetChristine Favre‐GuilmardMarie‐Noelle RocherJulien BindlerStéphanie WagnerEmile AndriambelosonBrian B. RudkinRudy MartyAlban VignaudMatthew BeardStephane LezmiMikhail KalinichevWileyarticlebotulinummuscleneurotoxinrecombinantrodentSNAP25Therapeutics. PharmacologyRM1-950ENPharmacology Research & Perspectives, Vol 9, Iss 5, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	botulinum muscle neurotoxin recombinant rodent SNAP25 Therapeutics. Pharmacology RM1-950
spellingShingle	botulinum muscle neurotoxin recombinant rodent SNAP25 Therapeutics. Pharmacology RM1-950 Cindy Périer Vincent Martin Sylvie Cornet Christine Favre‐Guilmard Marie‐Noelle Rocher Julien Bindler Stéphanie Wagner Emile Andriambeloson Brian B. Rudkin Rudy Marty Alban Vignaud Matthew Beard Stephane Lezmi Mikhail Kalinichev Recombinant botulinum neurotoxin serotype A1 in vivo characterization
description	Abstract Clinically used botulinum neurotoxins (BoNTs) are natural products of Clostridium botulinum. A novel, recombinant BoNT type A1 (rBoNT/A1; IPN10260) has been synthesized using the native amino acid sequence expressed in Escherichia coli and has previously been characterized in vitro and ex vivo. Here, we aimed to characterize rBoNT/A1 in vivo and evaluate its effects on skeletal muscle. The properties of rBoNT/A1 following single, intramuscular administration were evaluated in the mouse and rat digit abduction score (DAS) assays and compared with those of natural BoNT/A1 (nBoNT/A1). rBoNT/A1‐injected tibialis anterior was assessed in the in situ muscle force test in rats. rBoNT/A1‐injected gastrocnemius lateralis (GL) muscle was assessed in the compound muscle action potential (CMAP) test in rats. The rBoNT/A1‐injected GL muscle was evaluated for muscle weight, volume, myofiber composition and immunohistochemical detection of cleaved SNAP25 (c‐SNAP25). Results showed that rBoNT/A1 and nBoNT/A1 were equipotent and had similar onset and duration of action in both mouse and rat DAS assays. rBoNT/A1 caused a dose‐dependent inhibition of muscle force and a rapid long‐lasting reduction in CMAP amplitude that lasted for at least 30 days. Dose‐dependent reductions in GL weight and volume and increases in myofiber atrophy were accompanied by immunohistochemical detection of c‐SNAP25. Overall, rBoNT/A1 and nBoNT/A1 exhibited similar properties following intramuscular administration. rBoNT/A1 inhibited motoneurons neurotransmitter release, which was robust, long‐lasting, and accompanied by cleavage of SNAP25. rBoNT/A1 is a useful tool molecule for comparison with current natural and future modified recombinant neurotoxins products.
format	article
author	Cindy Périer Vincent Martin Sylvie Cornet Christine Favre‐Guilmard Marie‐Noelle Rocher Julien Bindler Stéphanie Wagner Emile Andriambeloson Brian B. Rudkin Rudy Marty Alban Vignaud Matthew Beard Stephane Lezmi Mikhail Kalinichev
author_facet	Cindy Périer Vincent Martin Sylvie Cornet Christine Favre‐Guilmard Marie‐Noelle Rocher Julien Bindler Stéphanie Wagner Emile Andriambeloson Brian B. Rudkin Rudy Marty Alban Vignaud Matthew Beard Stephane Lezmi Mikhail Kalinichev
author_sort	Cindy Périer
title	Recombinant botulinum neurotoxin serotype A1 in vivo characterization
title_short	Recombinant botulinum neurotoxin serotype A1 in vivo characterization
title_full	Recombinant botulinum neurotoxin serotype A1 in vivo characterization
title_fullStr	Recombinant botulinum neurotoxin serotype A1 in vivo characterization
title_full_unstemmed	Recombinant botulinum neurotoxin serotype A1 in vivo characterization
title_sort	recombinant botulinum neurotoxin serotype a1 in vivo characterization
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/08d7dae9cde34694bf838b65c8d1a5b6
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_version_	1718426462833344512

Recombinant botulinum neurotoxin serotype A1 in vivo characterization

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