RARE DISEASE
Botulism
Botulism
Botulism
Drug discovery
2
drugs
With orphan designations
Overview
Botulism is a neuroparalytic illness caused by potent neurotoxins produced by Clostridium botulinum and related species, characterized by symmetric descending flaccid paralysis beginning with cranial nerve deficits. It manifests through five transmission routes: foodborne (improperly preserved foods), wound (contaminated injuries/drug use), infant (intestinal colonization), iatrogenic (excessive botulinum toxin injections), and adult intestinal toxemia. Early antitoxin administration and intensive respiratory support are critical, as untreated cases progress to respiratory failure with 5-10% mortality [1][4][12].
Categories: rare infectious diseases, rare neurological diseases, rare ophthalmic disorders
Research Papers
1,358 drug discovery papers about Botulism, with 2 first-in-class and 33 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,358 drug discovery papers about Botulism, with 2 first-in-class and 33 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-28 | A single-case foodborne botulism outbreak caused by Clostridium botulinum type A1(B5) in diced garlic in Newfoundland and Labrador, 2024.
Foodborne botulism is a severe neuroparalytic disease caused by ingestion of foods containing botulinum neurotoxins, produced by Clostridium botulinum. In 2024, a 74-year-old woman from Newfoundland and Labrador with complete bilateral flaccid paralysis and respiratory distress was hospitalized and required intubation. From the broader differential diagnosis list, botulism was favoured prior to laboratory confirmation. Serum and feces samples initially tested negative for botulinum neurotoxins by mouse bioassay, yet viable C. botulinum type A was recovered from the feces. Food history investigation included some diced garlic in a repurposed coffee container that tested negative for botulinum neurotoxins by mouse bioassay, but viable C. botulinum type A was recovered from the sample. Both the fecal and garlic enrichment cultures were positive for bont/A and bont/B genes by real-time PCR. Whole genome sequencing revealed that both fecal and garlic isolates were highly similar with conserved gene synteny, including an intact bont/A1 gene and a disrupted (silent) bont/B5 gene encoded on the chromosome. This single-case foodborne botulism outbreak from Newfoundland and Labrador in 2024 was caused by C. botulinum type A1(B5) in diced garlic.
2026-06-25 | Establishment of two Hypotheses for Gut Bacterial Alteration Process for Minimizing the Intestinal Communicable Diseases.
Intestinal communicable diseases like diarrhea, dysentery, nausea, vomiting, cholera, typhoid fever, paratyphoid fever, botulism, gastroenteritis, etc., are caused by different microbes. Intestinal microbial ecology is the most mysterious and complex environment for microbes. Bacteriophages are the dominant viruses in the intestinal microbiota. It is well established that gut microbial composition directly affects human health. Microbes use the gastrointestinal tract as niches there some factors or theories exist such as dietary, quorum sensing, and biosignaling, including biomass and biofilm production. Whereas if some microbial disbalance happens due to the effect of antibiotics or different toxin production or uninterrupted and unexpected factors dysbiosis occurs. The outcome of dysbiosis is different communicable diseases in the intestine. Alteration in microbiota can make crucial improvements in the microbiota environment and to the body's health. After reviewing evidence authors are of the opinion that two natural microbial phenomena that may be utilized as a hypothetical approach to prevent communicable diseases in the intestine, i.e., microbes-microbes competition strategy and introduction of bacteriophage to kill the target bacteria in the gut.
2026-06-17 | When BAT Precedes BIG-IV in Infant Botulism: The Need for Structured Antitoxin Decision-Pathway Reporting in Case Reports.
In infant botulism, use of equine-derived botulinum antitoxin before BIG-IV may be clinically justified when the infant-specific product is delayed. Future case reports should document the treatment decision pathway, antitoxin timing, risk-benefit justification, guardian counseling, adverse-event monitoring, and relapse-prevention rationale to make such emergency decisions reproducible.
2026-05-25 | Foodborne Botulism in an Immunocompetent Adult Following the Consumption of a Prepackaged Soup.
Botulism is a potentially fatal neuroparalytic disease that has historically been associated with outbreaks from improperly stored foods. Today, foodborne botulism in adults is rare. Because of its rarity, early symptoms may go unrecognized, leading to rapid disease progression. Prompt recognition and early administration of antitoxin are critical, as there is currently no agent that reverses the neurological damage caused by the toxin. In this case, botulism was associated with the consumption of a commercially prepackaged, non-canned soup, rather than the classic association with improperly canned foods. We also highlight the importance of early recognition and the diagnostic challenges in differentiating botulism from other neuroparalytic disorders.
2026-05-20 | Development of novel 2-[(8-hydroxyquinolin-7-yl)(phenyl)methylamino]benzoic acid derivatives for inhibiting the catalytic activity of botulinum neurotoxins type B and F: in silico, in vitro & in vivo evaluation.
Botulinum neurotoxins (BoNTs) are the most pernicious toxin and category 'A' bioterrorism agent, responsible for 'botulism', a rare but fatal disease. Toxins are divided into seven toxinotypes from A-G, where A, B, E, and F are accountable for human botulism. The available treatment strategies are inadequate and ineffective for post-neuronal intoxication. We report novel 2-[(8-hydroxyquinolin-7-yl)(phenyl)methylamino]benzoic acid derivatives targetingthe catalytic site of VAMP-acting serotypes (BoNT/B and F). Inhibitory potential of the synthesized compounds was studied using a framework of in silico and experimental approaches. Inhibitory activity and binding affinity were evaluated using substrate-based cleavage and SPR assays. Compound efficacy was tested in mice through pre-mixed, prophylactic, and therapeutic strategies. Molecular dynamics simulations analyzed binding interactions, structural fluctuations, and complex stability. Endopeptidase assay revealed that the selected compounds displayed ≥ 80% inhibition of BoNT/B and F catalytic activity, with IC50 values ranging from 17.58 to 34.05 µM. SPR analysis displayed binding affinity of these molecules ranging from 8.13E-06 to 7.69E-04 for both the proteins. In the mouse bioassay, the selected molecules displayed complete protection and extension in survival of up to 20-fold. MD simulation study supported the experimental finding, revealing key interactions with HExxH and other active site residues forming stable conformation throughout the simulation time. Among them, compounds A15 and A36 were predicted to be more effective inhibitors of BoNT/B and F serotypes, respectively. These findings could lay a promising way for the development of novel therapeutics by reducing disease severity, enhancing survivability, and recovery where no post-exposure therapy presently available.
2026-07-28 | A single-case foodborne botulism outbreak caused by Clostridium botulinum type A1(B5) in diced garlic in Newfoundland and Labrador, 2024.
Foodborne botulism is a severe neuroparalytic disease caused by ingestion of foods containing botulinum neurotoxins, produced by Clostridium botulinum. In 2024, a 74-year-old woman from Newfoundland and Labrador with complete bilateral flaccid paralysis and respiratory distress was hospitalized and required intubation. From the broader differential diagnosis list, botulism was favoured prior to laboratory confirmation. Serum and feces samples initially tested negative for botulinum neurotoxins by mouse bioassay, yet viable C. botulinum type A was recovered from the feces. Food history investigation included some diced garlic in a repurposed coffee container that tested negative for botulinum neurotoxins by mouse bioassay, but viable C. botulinum type A was recovered from the sample. Both the fecal and garlic enrichment cultures were positive for bont/A and bont/B genes by real-time PCR. Whole genome sequencing revealed that both fecal and garlic isolates were highly similar with conserved gene synteny, including an intact bont/A1 gene and a disrupted (silent) bont/B5 gene encoded on the chromosome. This single-case foodborne botulism outbreak from Newfoundland and Labrador in 2024 was caused by C. botulinum type A1(B5) in diced garlic.
2026-06-25 | Establishment of two Hypotheses for Gut Bacterial Alteration Process for Minimizing the Intestinal Communicable Diseases.
Intestinal communicable diseases like diarrhea, dysentery, nausea, vomiting, cholera, typhoid fever, paratyphoid fever, botulism, gastroenteritis, etc., are caused by different microbes. Intestinal microbial ecology is the most mysterious and complex environment for microbes. Bacteriophages are the dominant viruses in the intestinal microbiota. It is well established that gut microbial composition directly affects human health. Microbes use the gastrointestinal tract as niches there some factors or theories exist such as dietary, quorum sensing, and biosignaling, including biomass and biofilm production. Whereas if some microbial disbalance happens due to the effect of antibiotics or different toxin production or uninterrupted and unexpected factors dysbiosis occurs. The outcome of dysbiosis is different communicable diseases in the intestine. Alteration in microbiota can make crucial improvements in the microbiota environment and to the body's health. After reviewing evidence authors are of the opinion that two natural microbial phenomena that may be utilized as a hypothetical approach to prevent communicable diseases in the intestine, i.e., microbes-microbes competition strategy and introduction of bacteriophage to kill the target bacteria in the gut.
2026-06-17 | When BAT Precedes BIG-IV in Infant Botulism: The Need for Structured Antitoxin Decision-Pathway Reporting in Case Reports.
In infant botulism, use of equine-derived botulinum antitoxin before BIG-IV may be clinically justified when the infant-specific product is delayed. Future case reports should document the treatment decision pathway, antitoxin timing, risk-benefit justification, guardian counseling, adverse-event monitoring, and relapse-prevention rationale to make such emergency decisions reproducible.
2026-05-25 | Foodborne Botulism in an Immunocompetent Adult Following the Consumption of a Prepackaged Soup.
Botulism is a potentially fatal neuroparalytic disease that has historically been associated with outbreaks from improperly stored foods. Today, foodborne botulism in adults is rare. Because of its rarity, early symptoms may go unrecognized, leading to rapid disease progression. Prompt recognition and early administration of antitoxin are critical, as there is currently no agent that reverses the neurological damage caused by the toxin. In this case, botulism was associated with the consumption of a commercially prepackaged, non-canned soup, rather than the classic association with improperly canned foods. We also highlight the importance of early recognition and the diagnostic challenges in differentiating botulism from other neuroparalytic disorders.
2026-05-20 | Development of novel 2-[(8-hydroxyquinolin-7-yl)(phenyl)methylamino]benzoic acid derivatives for inhibiting the catalytic activity of botulinum neurotoxins type B and F: in silico, in vitro & in vivo evaluation.
Botulinum neurotoxins (BoNTs) are the most pernicious toxin and category 'A' bioterrorism agent, responsible for 'botulism', a rare but fatal disease. Toxins are divided into seven toxinotypes from A-G, where A, B, E, and F are accountable for human botulism. The available treatment strategies are inadequate and ineffective for post-neuronal intoxication. We report novel 2-[(8-hydroxyquinolin-7-yl)(phenyl)methylamino]benzoic acid derivatives targetingthe catalytic site of VAMP-acting serotypes (BoNT/B and F). Inhibitory potential of the synthesized compounds was studied using a framework of in silico and experimental approaches. Inhibitory activity and binding affinity were evaluated using substrate-based cleavage and SPR assays. Compound efficacy was tested in mice through pre-mixed, prophylactic, and therapeutic strategies. Molecular dynamics simulations analyzed binding interactions, structural fluctuations, and complex stability. Endopeptidase assay revealed that the selected compounds displayed ≥ 80% inhibition of BoNT/B and F catalytic activity, with IC50 values ranging from 17.58 to 34.05 µM. SPR analysis displayed binding affinity of these molecules ranging from 8.13E-06 to 7.69E-04 for both the proteins. In the mouse bioassay, the selected molecules displayed complete protection and extension in survival of up to 20-fold. MD simulation study supported the experimental finding, revealing key interactions with HExxH and other active site residues forming stable conformation throughout the simulation time. Among them, compounds A15 and A36 were predicted to be more effective inhibitors of BoNT/B and F serotypes, respectively. These findings could lay a promising way for the development of novel therapeutics by reducing disease severity, enhancing survivability, and recovery where no post-exposure therapy presently available.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Botulism, including 1 approved therapy.
2 orphan drug designations for Botulism, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
recombinant botulinum vaccine A/B | vaccines | FDA | 2019-02-26 | — | The Surgeon General, Department of the Army |
botulism antitoxin heptavalent (A, B, C, D, E, F, G) (Equine) | antibodies | FDA | 2011-06-29 | 2013-03-22 | Cangene Corporation |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.