Botulinum Toxins: Old and New Applications in Humans and Animals for the Treatment of Lower Urinary Tract Conditions

Dear Colleagues,

Seven subtypes of botulinum toxin exist, named A–G, from which only two have been tested in the lower urinary tract and only one, subtype A (BoNT/A), has found its way to clinical application. BoNT/A is available in several different brands with different potencies, which has led the authorities to name them as ona-, abo-, and inco-botulinumtoxinA. To date, only onabotulinumtoxinA has been investigated in NDO and OAB in well-powered trials and licensed for those conditions. However, pivotal trials with the other brands are on their way, and results should be reported soon. Nevertheless, off-label use of abo- and incobotulinumtoxinA in other lower urinary tract conditions is common in urological practice.

The approved form of BoNT/A delivery is through multiple bladder wall injections. The number of punctures and the best place to inject has been the object of several studies, but firm conclusions allowing a reduction of injection points are still lacking. Methods intended to avoid the injection paradigm, in particular the liposomal carrier, seem to have failed. The mechanism of action includes the impairment of cholinergic and sensory nerve terminals and the blockade of the exocrine function of urothelial cells. According to clinical indication, some points of action may be more relevant, linked to the concept of nerve specific botulinum toxins. Direct injection in the central nervous system in lieu of bladder injections, investigated in animal models, has provided stimulating results.

In addition to neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), onabotulinumtoxinA has been investigated for the treatment of lower urinary tract symptoms in men with benign prostate hyperplasia and to relief pain in patients suffering from bladder pain syndrome/interstitial cystitis (BPS/IC). Phase 3 trials, which investigated BoNT/A injection in the prostate, failed to demonstrate a superiority over the placebo. The indication for BPS/IC is under investigation in several centers and, despite the different methods of bladder administration, seems to improve bladder pain. Large phase 3 trials are eagerly awaited.   

After an intense period of research in the beginning of the century, BoNT/A slowly left the spotlight of urological research. However, its common use in urological practice justifies a review of the advances in terms of mechanisms of action, mode of administration, and the situation of BoNT/A in licensed and off-label indications.

Prof. Francisco Cruz
Prof. Dr. Hann-Chorng Kuo
Guest Editors

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