Microbial toxins (botulinum)

Botulinum neutotoxins (BoNTs) are produced by the anaerobic bacterium Clostridium botulinum and are the most poisonous substances known in nature. Following entry into the circulation, BoNTs block neuro-transmission across neuromuscular junctions leading to systemic flaccid paralysis that may lead to respiratory failure and death. 

Currently, the only approved therapy for botulism is antitoxin collected from hyper-immune horses. A pharmaceutical grade antitoxin is manufactured at the Department of Biotechnology, IIBR. R&D in this field focused on developing and production of recombinant toxin-fragments that are rich in neutralizing epitopes. Scientists at the institute developed animal models to evaluate the efficacy of antitoxins as well as of novel therapeutics that are intended to be effective at late stages of the disease. The effect of homologous vs. heterologous antitoxins on treatment efficacy was thoroughly studied both for olygoclonal and for polyclonal antibody preparations.

Diagnosis of b​otulism relies on detection of the toxin in clinical samples. The gold-standard assay for this purpose is the mouse bioassay that takes 96 hours to complete and whose sensitivity is limited. Scientists at IIBR have developed an in vitro assay, the Endopep-MS assay, that can be completed in a few hours and is significantly more sensitive than the mouse bioassay. The utility of the assay was demonstrated in a clinical case of infant botulism where positive results were reported to the​ clinic within an intervention-relevant timeframe, and days before results could be obtained from the mouse bioassay, which eventually failed to detect the low levels of toxin.