The Biomedical Advanced Research and Development Authority (BARDA) is accepting submissions from therapeutic developers for preclinical testing services to advanced botulinum neurotoxin (BoNT) therapeutics and help bolster national preparedness against biological threats.
Demonstrating a therapeutic candidate’s effectiveness can be challenging due to the costs associated with testing. The BoNT-CTSS studies will be performed confidentially by one of BARDA’s nonclinical network providers at no cost to participants. While no direct financial support is available through this testing service, control data and product-specific data will be shared with participants and can be published in collaboration with BARDA.
Candidate therapeutics selected for testing will be evaluated for efficacy against up to four BoNT serotypes in preclinical pre- and/or post-intoxication models of botulism.
Candidates may include small molecules, antibodies, and other biologics, and study designs will be discussed in collaboration with the developer. After evaluation in BoNT-CTSS, candidates of interest could be considered for advanced development by BARDA.
BARDA will accept candidates on an ongoing basis. Researchers from academic institutions, industry, and government institutions are eligible to apply.
Additional information about this program, including a full list of eligibility requirements, is available at BARDA’s CBRN Antivirals and Antitoxins Medical Countermeasures Program webpage.
The bacterial toxins such as botulinum, conotoxins, Clostridium perfrigens, epsilson toxin, saxitoxins, shigatoxins, tetrodotoxins, can be used in bioterrorism due to high toxicity and short incubation time. The promising role of nanomaterial’s in the detection of bacterial toxins is summarized highlighting their advantages, need principles, and limitations in terms of sensitivity, accuracy, simplicity, sensitivity, cost effectiveness and multiplexing capability. (Poisoning – Prevention, Diagnosis, Treatment and Poison Repurposing Jan 2024)
Botulinum neurotoxins are the most poisonous substances reported and listed in category ‘A’ of biowarfare agent. These neurotoxins cause flaccid paralysis of muscles by inhibiting acetylcholine release at the neuromuscular junction, and leads to death. The light chain (catalytic domain) is responsible for cleavage of SNAREs and inhibition of its activity stops the progress of neuroparalysis. Serotype identification is a time-consuming process; hence development of inhibitor against human botulism causing serotypes will be advantageous. In present study, ligand-based in silico method was applied to identify the “hits” against human intoxicating BoNTs based on their binding affinities and ADMET analysis. A computational approach for docking 35 designed ligands to the catalytic domain of serotype BoNT/A; B; E and F, using Molegro Virtual Docker and AutoDock suite was performed. (Europe PMC)
Currently, there is a lack of effective countermeasures to combat BoNT intoxication in the event of a biological attack. Here researchers report on a novel solution by combining cell metabolic engineering with cell membrane coating nanotechnology, resulting in the development of glycan-modified cellular nanosponges that serve as a biomimetic and broad-spectrum BoNT detoxification strategy. The team increased the expression levels of gangliosides on THP-1 cells through metabolic engineering, and then collect the modified THP-1 cell membrane and coat it onto synthetic polymeric cores, creating cellular nanosponges that closely mimic host cells. Findings demonstrate that higher levels of gangliosides on the cellular nanosponges result in greater binding capacities with BoNT. (Biomaterials Nov 2023)
There has been little research about bispecific antibodies in the passive immunotherapy of BoNT/A. Here researchers aimed to construct a bispecific antibody (termed LUZ-A1-A3) based on the anti-BoNT/A human monoclonal antibodies (HMAb) A1 and A3. LUZ-A1-A3 binds to the Hc and L-HN domains of BoNT/A, displaying potent neutralization activity against BoNT/A (124 × higher than that of HMAb A1 or HMAb A3 alone and 15 × higher than that of the A1 + A3 combination). (Nature – Nov 2023)