Botulinum neurotoxin a receptor and the use thereof
The present invention is based on the identification of synaptic vessel glycoprotein SV2 as the BoNT/A receptor and the further identification of various BoNT/A-binding fragments of SV2. The disclosure here provides new tools for diagnosing and treating botulism.
1. A method for reducing botulinum neurotoxin A (BoNT/A) toxicity in a human or non-human animal comprising the step of:
administering to the human or non-human animal an agent that reduces binding between BoNT/A and synaptic vesicle glycoprotein 2 (SV2) in the human or non-human animal, wherein the agent is capable of binding to BoNT/A and is a polypeptide comprising an amino acid sequence selected from the group consisting of (i) amino acids 529-566 of rat SV2C (SEQ ID NO:6), (ii) amino acids 529-566 of human SV2C (SEQ ID NO:18), (iii) amino acids 486 to 523 of rat SV2B (SEQ ID NO:4), (iv) amino acids 486 to 523 of mouse SV2B (SEQ ID NO:10), (v) amino acids 543 to 576 of rat SV2A (SEQ ID NO:2), (vi) amino acids 454 to 580 of rat SV2C (SEQ ID NO:6), (vii) amino acids 454 to 580 of human SV2C (SEQ ID NO:18), (viii) amino acids 411 to 536 of rat SV2B (SEQ ID NO:4), (ix) amino acids 411 to 536 of mouse SV2B (SEQ ID NO:10), (x) amino acids 468 to 595 of rat SV2A (SEQ ID NO:2), and (xi) amino acids 468 to 595 of human SV2A (SEQ ID NO:14).
2. The method of claim 1 , wherein the method is for reducing BoNT/A toxicity in a human.
3. The method of claim 1 , wherein the agent further comprises a ganglioside.