A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism
Antitoxin, the only licensed drug therapy for botulism, neutralizes circulating botulinum neurotoxin (BoNT). However, antitoxin is no longer effective when a critical amount of BoNT has already entered its target nerve cells. The outcome is a chronic phase of botulism that is characterized by prolon...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/10/679 |
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| author | Amram Torgeman Eran Diamant Eyal Dor Arieh Schwartz Tzadok Baruchi Alon Ben David Ran Zichel |
| author_facet | Amram Torgeman Eran Diamant Eyal Dor Arieh Schwartz Tzadok Baruchi Alon Ben David Ran Zichel |
| author_sort | Amram Torgeman |
| collection | DOAJ |
| description | Antitoxin, the only licensed drug therapy for botulism, neutralizes circulating botulinum neurotoxin (BoNT). However, antitoxin is no longer effective when a critical amount of BoNT has already entered its target nerve cells. The outcome is a chronic phase of botulism that is characterized by prolonged paralysis. In this stage, blocking toxin activity within cells by next-generation intraneuronal anti-botulinum drugs (INABDs) may shorten the chronic phase of the disease and accelerate recovery. However, there is a lack of adequate animal models that simulate the chronic phase of botulism for evaluating the efficacy of INABDs. Herein, we report the development of a rabbit model for the chronic phase of botulism, induced by intoxication with a sublethal dose of BoNT. Spirometry monitoring enabled us to detect deviations from normal respiration and to quantitatively define the time to symptom onset and disease duration. A 0.85 rabbit intramuscular median lethal dose of BoNT/A elicited the most consistent and prolonged disease duration (mean = 11.8 days, relative standard deviation = 27.9%) that still enabled spontaneous recovery. Post-exposure treatment with antitoxin at various time points significantly shortened the disease duration, providing a proof of concept that the new model is adequate for evaluating novel therapeutics for botulism. |
| first_indexed | 2024-03-10T06:10:09Z |
| format | Article |
| id | doaj.art-1b12d34b698546479985911a5bf24792 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T06:10:09Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-1b12d34b698546479985911a5bf247922023-11-22T20:12:47ZengMDPI AGToxins2072-66512021-09-01131067910.3390/toxins13100679A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of BotulismAmram Torgeman0Eran Diamant1Eyal Dor2Arieh Schwartz3Tzadok Baruchi4Alon Ben David5Ran Zichel6Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, IsraelDepartment of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, IsraelDepartment of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, IsraelDepartment of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, IsraelDepartment of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, IsraelDepartment of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, IsraelDepartment of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, IsraelAntitoxin, the only licensed drug therapy for botulism, neutralizes circulating botulinum neurotoxin (BoNT). However, antitoxin is no longer effective when a critical amount of BoNT has already entered its target nerve cells. The outcome is a chronic phase of botulism that is characterized by prolonged paralysis. In this stage, blocking toxin activity within cells by next-generation intraneuronal anti-botulinum drugs (INABDs) may shorten the chronic phase of the disease and accelerate recovery. However, there is a lack of adequate animal models that simulate the chronic phase of botulism for evaluating the efficacy of INABDs. Herein, we report the development of a rabbit model for the chronic phase of botulism, induced by intoxication with a sublethal dose of BoNT. Spirometry monitoring enabled us to detect deviations from normal respiration and to quantitatively define the time to symptom onset and disease duration. A 0.85 rabbit intramuscular median lethal dose of BoNT/A elicited the most consistent and prolonged disease duration (mean = 11.8 days, relative standard deviation = 27.9%) that still enabled spontaneous recovery. Post-exposure treatment with antitoxin at various time points significantly shortened the disease duration, providing a proof of concept that the new model is adequate for evaluating novel therapeutics for botulism.https://www.mdpi.com/2072-6651/13/10/679botulinumchronicsublethalantitoxinanimal model |
| spellingShingle | Amram Torgeman Eran Diamant Eyal Dor Arieh Schwartz Tzadok Baruchi Alon Ben David Ran Zichel A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism Toxins botulinum chronic sublethal antitoxin animal model |
| title | A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism |
| title_full | A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism |
| title_fullStr | A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism |
| title_full_unstemmed | A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism |
| title_short | A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism |
| title_sort | rabbit model for the evaluation of drugs for treating the chronic phase of botulism |
| topic | botulinum chronic sublethal antitoxin animal model |
| url | https://www.mdpi.com/2072-6651/13/10/679 |
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