Pharmaceuticals & Vitamin D : Biodefense


Protein Receptors for Botulinum Neurotoxin E (BoNT/E) Enable Means of Reducing BoNT/E Toxicity

UW-Madison researchers have identified the mechanism of BoNT/E entry into neurons.  They found that two glycosylated isoforms of the synaptic vesicle protein SV2, in conjunction with gangliosides, mediate the entry of BoNT/E into neurons.  The two isoforms of SV2, SV2A and SV2B, are the protein receptors for BoNT/E.  Specifically, the L4 domain of SV2A and SV2B mediates BoNT/E entry and is sufficient to act as the toxin binding site on neuronal surfaces.

This discovery provides a means of reducing BoNT/E toxicity by administering an agent that inhibits binding between BoNT/E and SV2A or SV2B.  It allows specific anti-toxins against BoNT/E to be prepared more readily.  It also enables screening for agents that inhibit BoNT toxin or block binding between BoNT/E and SV2A or SV2B.

Receptor For Bacillus anthracis Toxin

UW-Madison researchers have now provided the structure and sequence of the anthrax toxin receptor. The complete receptor includes an extracellular domain, a transmembrane domain and a cytoplasmic domain that can vary in length.

Identification of the sequence of the anthrax toxin receptor (ATR) will enable the detection and quantification of ATR mRNA and protein in a sample, and will also allow the generation of transgenic and knockout animals. This should lead to methods for treating human and non-human animals suffering from anthrax. For example, the inventors have demonstrated the therapeutic effectiveness of this invention by showing in tissue culture models that a soluble form of the receptor can block anthrax toxin by acting like a decoy.

Method of Targeting Pharmaceuticals to Motor Neurons

UW-Madison researchers have developed a method for delivering therapeutic drugs to motor neurons. This method could be used to treat botulism, which is caused by botulinum neurotoxin, a potentially serious biological warfare agent. It involves synthesizing a therapeutic molecule covalently bound to a polymeric delivery vehicle and conjugating it to a botulinum neurotoxin heavy chain. The botulinum neurotoxin heavy chain acts as a vehicle for delivery of pharmaceuticals to motor neurons.