Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins

All the botulinum type A neurotoxins available for clinical use are of the A1 subtype. We developed a subtype A2 low-molecular-weight (150 kD (kilo Dalton)) neurotoxin (A2NTX) with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies s...

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Autores principales: Toshiaki Takeuchi, Tsuyoshi Okuno, Ai Miyashiro, Tomoko Kohda, Ryosuke Miyamoto, Yuishin Izumi, Shunji Kozaki, Ryuji Kaji
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:9a9ff29f6a3843ac893cb75e843cbfad2021-11-25T19:09:11ZClinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins10.3390/toxins131108242072-6651https://doaj.org/article/9a9ff29f6a3843ac893cb75e843cbfad2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6651/13/11/824https://doaj.org/toc/2072-6651All the botulinum type A neurotoxins available for clinical use are of the A1 subtype. We developed a subtype A2 low-molecular-weight (150 kD (kilo Dalton)) neurotoxin (A2NTX) with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed that its efficacy is superior to A1 toxins. We conducted an open study exploring its safety and tolerability profile in comparison with A1LL (LL type A1 toxin, or onabotulinumtoxinA) and a low-molecular-weight (150 kD) A1 neurotoxin (A1NTX). Those who had been using A1LL (<i>n</i> = 90; 50–360 mouse LD50 units) or A1NTX (<i>n</i> = 30; 50–580 units) were switched to A2NTX (<i>n</i> = 120; 25–600 units) from 2010 to 2018 (number of sessions ~27, cumulative doses ~11,640 units per patient). The adverse events for A2NTX included weakness (<i>n</i> = 1, ascribed to alcoholic polyneuropathy), dysphagia (1), local weakness (4), and spread to other muscles (1), whereas those for A1LL or A1NTX comprised weakness (<i>n</i> = 2, A1NTX), dysphagia (8), ptosis (6), local weakness (7), and spread to other muscles (15). After injections, 89 out of 120 patients preferred A2NTX to A1 for the successive sessions. The present study demonstrated that A2NTX had clinical safety up to the dose of 500 units and was well tolerated compared to A1 toxins.Toshiaki TakeuchiTsuyoshi OkunoAi MiyashiroTomoko KohdaRyosuke MiyamotoYuishin IzumiShunji KozakiRyuji KajiMDPI AGarticlebotulinum toxinsubtype A2clinical tolerabilitysafetypatientsMedicineRENToxins, Vol 13, Iss 824, p 824 (2021)
institution DOAJ
collection DOAJ
language EN
topic botulinum toxin
subtype A2
clinical tolerability
safety
patients
Medicine
R
spellingShingle botulinum toxin
subtype A2
clinical tolerability
safety
patients
Medicine
R
Toshiaki Takeuchi
Tsuyoshi Okuno
Ai Miyashiro
Tomoko Kohda
Ryosuke Miyamoto
Yuishin Izumi
Shunji Kozaki
Ryuji Kaji
Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins
description All the botulinum type A neurotoxins available for clinical use are of the A1 subtype. We developed a subtype A2 low-molecular-weight (150 kD (kilo Dalton)) neurotoxin (A2NTX) with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed that its efficacy is superior to A1 toxins. We conducted an open study exploring its safety and tolerability profile in comparison with A1LL (LL type A1 toxin, or onabotulinumtoxinA) and a low-molecular-weight (150 kD) A1 neurotoxin (A1NTX). Those who had been using A1LL (<i>n</i> = 90; 50–360 mouse LD50 units) or A1NTX (<i>n</i> = 30; 50–580 units) were switched to A2NTX (<i>n</i> = 120; 25–600 units) from 2010 to 2018 (number of sessions ~27, cumulative doses ~11,640 units per patient). The adverse events for A2NTX included weakness (<i>n</i> = 1, ascribed to alcoholic polyneuropathy), dysphagia (1), local weakness (4), and spread to other muscles (1), whereas those for A1LL or A1NTX comprised weakness (<i>n</i> = 2, A1NTX), dysphagia (8), ptosis (6), local weakness (7), and spread to other muscles (15). After injections, 89 out of 120 patients preferred A2NTX to A1 for the successive sessions. The present study demonstrated that A2NTX had clinical safety up to the dose of 500 units and was well tolerated compared to A1 toxins.
format article
author Toshiaki Takeuchi
Tsuyoshi Okuno
Ai Miyashiro
Tomoko Kohda
Ryosuke Miyamoto
Yuishin Izumi
Shunji Kozaki
Ryuji Kaji
author_facet Toshiaki Takeuchi
Tsuyoshi Okuno
Ai Miyashiro
Tomoko Kohda
Ryosuke Miyamoto
Yuishin Izumi
Shunji Kozaki
Ryuji Kaji
author_sort Toshiaki Takeuchi
title Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins
title_short Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins
title_full Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins
title_fullStr Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins
title_full_unstemmed Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins
title_sort clinical safety and tolerability of a2ntx, a novel low-molecular-weight neurotoxin derived from botulinum neurotoxin subtype a2, in comparison with subtype a1 toxins
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/9a9ff29f6a3843ac893cb75e843cbfad
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