An Novel Medical System for Quantitative Diagnosis and Personalized Precision Botulinum Neurotoxin Injection in Chronic Pelvic Pain Management

Abstract Chronic pelvic pain (CPP) negatively impacts the social and sexual quality of life in up to 20% of women in the US. Interstitial cystitis/ bladder pain syndrome (IC/BPS), which affects 6.5% of women in the US, is one of the most debilitating CPP conditions. Pelvic floor overactivity (PFOA) is prevalent among patients with CPP and presents in up to 85% of women with IC/BPS. Conservative treatment strategies employ physical therapy interventions that include manual soft tissue mobilization, dilation, and muscle retraining. When conservative therapies fail, injection therapies may be indicated. Specifically, botulinum neurotoxin (BoNT, or onabotulinumtoxinA) has received growing interest in managing PFOA. BoNT blocks acetylcholine release, thereby inhibiting neuromuscular transmission at the neuromuscular junction (NMJ). By inhibiting neuromuscular transmission in spastic muscles, transient muscle relaxation commences, and pain is relieved. Despite its potency and safety, BoNT can cause dose-dependent adverse effects and is expensive. Studies have shown that increasing the injection distance by 1 cm away from the NMJs reduces the efficacy of BoNT by 46%. An NMJ-targeted precision BoNT injection technique will retain therapeutic effects, reduce adverse effects and cost. Unfortunately, an NMJ-targeted precision BoNT injection technique is not yet available. To address this gap in CPP management, we have 1) successfully developed a novel vaginal high-density surface electromyography (HD-sEMG) technique to reliably and quantitatively assess PFOA and accurately map the NMJ distributions of overactive pelvic floor muscles (PFMs), and 2) successfully demonstrated a significant improvement (66%) in BoNT injection treatment outcomes with vs. without HD-sEMG guidance. Inspired by the promising research results, the HillMed and the University of Houston PIs co-invented a novel technique for personalized BoNT injections, guided using vaginal HD-sEMG, for managing CPP and PFOA. This FastTrack SBIR project aims to develop a commercializable, personalized, precision BoNT injection medical device, i.e., the PelviMap, utilizing a vaginal HD-sEMG technology, to optimize the treatment outcomes in CPP management. In Phase I, we will develop the vaginal HD-sEMG probe to further improve its diagnostic performance, and develop PFOA severity assessment and NMJ mapping algorithms into a clinician-friendly automated software package, which will be fully integrated into the proposed PelviMap system. In Phase II, we will assess the efficacy of the developed personalized, precision BoNT injection medical device (PelviMap) in a clinical trial study with 46 women with IC/BPS, and 15 healthy controls in collaboration with Baylor College of Medicine. The deliverable of this proposal is to, for the first time, develop a marketed NMJ-targeted precision BoNT injection system to optimize the BoNT treatment efficiency in CPP management. Successful commercialization can help up to 26 million women who suffer from CPP and require more effective therapy.Project Narrative Chronic pelvic pain (CPP) is a debilitating condition that negatively impacts the social and sexual quality of life in up to 20% of American women. Botulinum neurotoxin (BoNT) has received growing interest in managing CPP, but it can cause dose-dependent side- effects and is expensive. This FastTrack SBIR project aims to develop a commercializable, personalized, precision BoNT injection medical device, i.e., the PelviMap system, implementing validated vaginal HD-sEMG technology to optimize the treatment outcomes in CPP management.