Botulinum neurotoxins (BoNTs) cause flaccid
paralysis by interfering with vesicle fusion and
neurotransmitter release in the neuronal cells. BoNTs are the most widely used therapeutic
proteins.
BoNT/A was approved by the U.S. FDA to treat
strabismus, blepharospam, and hemificial
spasm as early as 1989 and then for treatment of
cervical dystonia, glabellar facial lines, axillary
hyperhidrosis, chronic
migraine and for cosmetic use. Due to its high efficacy, longevity of action and satisfactory safety profile, it has been used empirically in a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, and painful disorders. Currently available BoNT
therapies are limited to neuronal indications with the requirement of periodic
injections resulting in immune-resistance for some indications. Recent understanding of the structure-function relationship of BoNTs prompted the engineering of novel BoNTs to extend therapeutic interventions in non-neuronal systems and to overcome the immune-resistance issue. Much research still needs to be done to improve and extend the medical uses of BoNTs.