The Unusual History and the Urological Applications of Botulinum Neurotoxin

Abstract

Introduction: Botulinum neurotoxin (BoNT) is probably the most potent biological toxin that can affect humans. Since its discovery by Justinus Kerner, BoNT has seen use in a wide range of cosmetic and non-cosmetic conditions such as cervical dystonia, cerebral palsy, migraines and hyperhidrosis. We tried to trace its history from its inception to its recent urological applications. Materials and Methods: Historical articles about botulinum toxin were reviewed and a Medline search was performed for its urological utility. We hereby present a brief review of historical aspects of BoNT and its applications in urology. Results: In 1793, the first known outbreak of botulism occurred due to ‘spoiled’ sausage in Wildebad, Germany. The German physician and poet Justinus Kerner published the first accurate description of the clinical symptoms of botulism (sausage poison). He was also the first to mention its potential therapeutic applications. In urology, BoNT has been used in bladder and urethral lesions with varying degree of success. Recently, BoNT applications were explained for prostatic disorders. BoNT applications in urology are in the treatment of detrusor external sphincter dyssynergia, detrusor overactivity, detrusor underactivity, spastic conditions of the urethral sphincter, chronic prostate pain, interstitial cystitis, non-fibrotic bladder outflow obstruction (including benign prostatic hyperplasia) and acute urinary retention in women. Conclusion: Justinus Kerner is the godfather of botulism research. The role of BoNT in urology has evolved exponentially and it is widely used as an adjuvant in voiding dysfunction. In the future, its utility will broaden and guide the urologist in managing various urological disorders.

Onabotulinum Toxin A (Botox®) in the Treatment of Neurogenic Bladder Overactivity

“…Remarkably, botulism was accurately and thoroughly described by Justinus Kerner at the beginning of the nineteenth century, although it was not until late in the same century that Van Ermengem described the bacterial basis, isolated and grew the causative anaerobic bacterium and described its toxin (5-7). During the following decades the toxin was isolated and described in greater detail, in addition the requirement for toxin inactivation by heat was identified.…”

“…Since then the toxin has been utilized in a surprisingly wide range of clinical conditions, including cerebral palsy, dystonia, torticollis, migraine, hyperhidrosis, oAB, etc. and has found a further extensive use in aesthetic dermatology (3, 5, 8-10). …”

“…Post-void residual volume may also frequently present a challenge, which can easily be solved by CIC (13, 29). The beneficial effects of the toxin remain after repeated injections, and the risk of developing bladder fibrosis following frequent treatment with BT-A has not been confirmed (5, 13, 19, 36-38). …”

“…The use of BT in urology was pioneered in the eighties with injection into the urethral sphincter, and during recent years the use of BT has revolutionized the treatment of intractable Do symptoms, while pelvic pain syndrome, benign prostatic diseases and bladder pain have also been included in possible indications for BT treatment (5). In the following, a review of the applicability of BT in the treatment of NDo is presented.…”

Kinetic and Reaction Pathway Analysis in the Application of Botulinum Toxin A for Wound Healing

“…As characterized by Hanchanale and coworkers [1], the perception of botulinum toxin A has been transformed “from poison to a healing agent.” Much of our present knowledge about this toxin comes from the toxicological literature. Information concerning botulinum neurotoxin serotypes, molecular structures, substrate specificities, mechanisms of zinc-dependent peptide hydrolysis, ion channel formation, and other detailed topics has been extensively reviewed [2–4].…”