Phase 1/2 onabotulinumtoxinA (BOTOX) neuromuscular blocker (SNARE-mediated ACh release inhibitor) in high-risk prostate cancer

This Phase 1/2 pilot from Houston Methodist (The Methodist Hospital Research Institute) randomizes 30 men 1:1 in a single-blind, placebo-controlled design to a one-time intraprostatic onabotulinumtoxinA injection (50 units) vs saline, given 6–8 weeks before radical prostatectomy. OnabotulinumtoxinA (Allergan/AbbVie) is a botulinum toxin type A that cleaves SNAP-25, blocking SNARE-dependent acetylcholine release from cholinergic nerve terminals and producing local chemodenervation; here it’s being repurposed as a biologic “microenvironment modulator” rather than a cytotoxic or androgen-axis therapy. The eligible population is high-risk localized prostate adenocarcinoma (including Gleason score ≥8). Readouts focus on feasibility and safety plus preliminary biologic/pathologic signals at prostatectomy and early postoperative PSA kinetics. The scientific/commercial angle is a locally delivered, non-oncology branded biologic being tested as a neoadjuvant adjunct; today’s care for high-risk localized disease is definitive local therapy (radical prostatectomy with lymph node evaluation or radiation) often combined with androgen-deprivation therapy and risk-adapted intensification, with neoadjuvant approaches still investigational.