Caister Academic Press

Botulinum Neurotoxins as Therapeutics

Sheng Chen
from: Bacterial Toxins: Genetics, Cellular Biology and Practical Applications (Edited by: Thomas Proft). Caister Academic Press, U.K. (2013)

Abstract

Botulinum neurotoxins (BoNTs) cause flaccid paralysis by interfering with vesicle fusion and neurotransmitter release in the neuronal cells. Due to their high efficacy, prolonged activity and satisfactory safety profile, BoNTs are now the most widely used therapeutic proteins. BoNT/A was approved by the U.S. FDA to treat strabismus, blepharospam, hemifacial spasm, cervical dystonia, glabellar facial lines, axillary hyperhidrosis and chronic migraine and for cosmetic use. The efficacy of BoNT/A in treating dystonia and other neuronal disorders, coupled with the satisfactory safety profile, has prompted its empirical use in a variety of indications. Currently available BoNT therapies have certain limitations such as the neuronal specific indications and immunoresistance issues resulting from periodic injections. Recent studies on the structure-function characterization of HCs and LCs of Botulinum Neurotoxins have advanced our knowledge on the mechanisms of BoNT receptor binding, internalization and substrate recognition. Advanced understanding in these areas has opened up new opportunities to engineer recombinant proteins to treat diseases that are not amenable to therapy with native neurotoxins, or to give better outcome than with the native neurotoxins. In conclusion, the future of BoNTs in medical applications is bright, yet more research is needed to improve their medical uses read more ...
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