ArticleJCI insight2020
Symptomatic treatment of botulism with a clinically approved small molecule.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Unveiling Novel Metalloprotease Inhibitors Targeting Botulinum Neurotoxin Through Structure-Based Virtual Screening of Drug Libraries and Molecular Dynamics Simulations.International journal of molecular sciences · 2026Article
- Equine botulism.Equine veterinary journal · 2026Review
- Combined treatment with antitoxin and 3,4-diaminopyridine improves survival outcomes after lethal botulinum neurotoxin challenge.Molecular medicine (Cambridge, Mass.) · 2025Article
- Investigations of Thiosemicarbazides as Botulinum Toxin Active-Site Inhibitors: Enzyme, Cellular, and Rodent Intoxication Studies.ACS infectious diseases · 2024Article
- The Degradation of Botulinum Neurotoxin Light Chains Using PROTACs.International journal of molecular sciences · 2024Article
- Aminopyridines Restore Ventilation and Reverse Respiratory Acidosis at Late Stages of Botulism in Mice.The Journal of pharmacology and experimental therapeutics · 2024Article
- 3,3-Disubstituted 3,4-Dihydro-1,2,4-benzotriazines: Chemistry, Biological Activity, and Affinity to Sigma Receptors.Molecules (Basel, Switzerland) · 2023Review
- Neuromuscular recovery from botulism involves multiple forms of compensatory plasticity.Frontiers in cellular neuroscience · 2023Article
- Intramuscular delivery of formulated RNA encoding six linked nanobodies is highly protective for exposures to three Botulinum neurotoxin serotypes.Scientific reports · 2022Article
- Antidotal treatment of botulism in rats by continuous infusion with 3,4-diaminopyridine.Molecular medicine (Cambridge, Mass.) · 2022Article
- Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update.Archives of toxicology · 2022Review
- rAAV expressing recombinant neutralizing antibody for the botulinum neurotoxin type A prophylaxis.Frontiers in microbiology · 2022Article
- Effects of 3,4-diaminopyridine on myasthenia gravis: Preliminary results of an open-label study.Frontiers in pharmacology · 2022Article
- Article
- Neuronal delivery of antibodies has therapeutic effects in animal models of botulism.Science translational medicine · 2021Article
- Screening of a Focused Ubiquitin-Proteasome Pathway Inhibitor Library Identifies Small Molecules as Novel Modulators of Botulinum Neurotoxin Type A Toxicity.Frontiers in pharmacology · 2021Article
- Camelid VHH Antibodies that Neutralize Botulinum Neurotoxin Serotype E Intoxication or Protease Function.Toxins · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Botulinum neurotoxins (BoNTs) are potent neuroparalytic toxins that cause mortality through respiratory paralysis. The approved medical countermeasure for BoNT poisoning is infusion of antitoxin immunoglobulins. However, antitoxins have poor therapeutic efficacy in symptomatic patients; thus, there is an urgent need for treatments that reduce the need for artificial ventilation. We report that the US Food and Drug Administration-approved potassium channel blocker 3,4-diaminopyridine (3,4-DAP) reverses respiratory depression and neuromuscular weakness in murine models of acute and chronic botulism. In ex vivo studies, 3,4-DAP restored end-plate potentials and twitch contractions of diaphragms isolated from mice at terminal stages of BoNT serotype A (BoNT/A) botulism. In vivo, human-equivalent doses of 3,4-DAP reversed signs of severe respiratory depression and restored mobility in BoNT/A-intoxicated mice at terminal stages of respiratory collapse. Multiple-dosing administration of 3,4-DAP improved respiration and extended survival at up to 5 LD50 BoNT/A. Finally, 3,4-DAP reduced gastrocnemius muscle paralysis and reversed respiratory depression in sublethal models of serotype A-, B-, and E-induced botulism. These findings make a compelling argument for repurposing 3,4-DAP to symptomatically treat symptoms of muscle paralysis caused by botulism, independent of serotype. Furthermore, they suggest that 3,4-DAP is effective for a range of botulism symptoms at clinically relevant time points.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.