{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T02:56:42Z","timestamp":1772765802972,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020594","name":"Israel Institute for Biological Research","doi-asserted-by":"publisher","award":["SB95"],"award-info":[{"award-number":["SB95"]}],"id":[{"id":"10.13039\/501100020594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/toxins13100679","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T23:08:31Z","timestamp":1632784111000},"page":"679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism"],"prefix":"10.3390","volume":"13","author":[{"given":"Amram","family":"Torgeman","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eran","family":"Diamant","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyal","family":"Dor","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arieh","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzadok","family":"Baruchi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alon","family":"Ben David","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-4901","authenticated-orcid":false,"given":"Ran","family":"Zichel","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1001\/jama.285.8.1059","article-title":"Botulinum toxin as a biological weapon: Medical and public health management","volume":"285","author":"Arnon","year":"2001","journal-title":"J. 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