Botulinum neurotoxin - from laboratory to bedside.
Botulinum neurotoxin (BoNT) has been used clinically since 1980, with an ever-increasing range of clinical applications. This has coincided with a period of massively expanded interest in the underlying biology of the neurotoxin. Tremendous advances have taken place in the scientific understanding of neurotoxin structure and function since the description of their endopeptidase activity in 1992. These developments have led to an increased understanding of the mechanisms underpinning the clinical use of the neurotoxins and also in the technologies available to support their clinical use. The expanding range of clinical applications, and use in increasing doses, has also generated challenges for the clinicians and manufacturers of BoNT preparations to ensure continuing efficacy and safety margins for these new clinical settings. To date the increased clinical use of BoNTs has occurred largely empirically, and not by application of the recent insights into neurotoxin structure and function. With the increased knowledge regarding the biology of the neurotoxins, however, there is the opportunity to select preferred forms of the toxin for particular clinical applications and even to consider engineering the neurotoxins to produce modified products more suited to specific clinical applications. These developments and opportunities that have arisen, particularly over the last decade, emphasise the increasing need to maintain an active two way dialogue between clinicians and basic scientists to ensure that the advances in the laboratory are translated into clinical benefit and that the clinical developments in use of neurotoxin are supported by the scientific research activity. This article is based upon presentations given in a workshop at the 5th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxin in Denver in June, 2005 seeking to address issues relating to the laboratory/clinic interface.