Gaining ground: assays for therapeutics against botulinum neurotoxin.
Owing in part to recently heightened concern over bioterrorism, interest in the mechanism of action of botulinum neurotoxin (BoNT) and development of effective therapeutic strategies has dramatically increased. The emergence of BoNT as an effective treatment for a variety of neurological disorders and its growing use in the cosmetic industry have also increased interest in developing effective countermeasures. Although recent attempts to create effective vaccines appear promising, the multitude of clinical and cosmetic uses of BoNT make mass vaccination against the toxin undesirable and impractical, leading to intensified efforts to develop effective therapeutics to combat large-scale intoxications. In this review, we examine the relevant and available in vitro cell-based assays and in vivo assays for drug discovery and development, especially with regard to the potential for medium- to high-throughput automation and its use in identifying physiologically relevant inhibitors.
Hakami
Ramin Mollaaghababa
RM
Faculty Research Participation Program, Oak Ridge Associated Universities, Belcamp, MD, USA. ramin.hakami@us.army.mil
Ruthel
Gordon
G
Stahl
Andrea M
AM
Bavari
Sina
S
D000818:Animals; D000992:Antitoxins / Q000032:analysis* / Q000627:therapeutic use; D001905:Botulinum Toxins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D001906:Botulism / Q000188:drug therapy*; D002460:Cell Line; D003014:Clostridium botulinum / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
D000992:Antitoxins; D009498:Neurotoxins; D001905:Botulinum Toxins