New Strategies to Treat Overactive Bladder

描述(申请人提供)：膀胱过度活动症(OAB)被国际大陆协会定义为一种以急迫性尿失禁为特征的综合征，通常伴有尿频和夜尿。在美国，约有3330万成年人患有OAB。女性OAB的总体患病率为16.9%，男性为16.2%。OAB对生活质量的影响是心理的、社会的和深刻的。抗鞭毛虫药物是一线药物治疗。然而，许多OAB患者由于其中等疗效和明显的不良反应，如口干、便秘、头痛和视力模糊，在6-12个月内退出抗肌松药治疗。另一种治疗方法是骶神经调节，仅在药物治疗失败后才提供给OAB患者。然而，由于其侵袭性、费用和对训练有素的外科医生的要求，骶神经调节的临床益处受到很大限制。目前，成功治疗OAB仍然是临床医生面临的一个治疗挑战。这项赠款申请的目标是开发新的战略来应对这一治疗挑战。我们假设电和药物神经调节的结合可以显著提高目前治疗OAB的疗效，并创造出更多患者可以接受的新的、有效的、非侵入性的治疗方法。第一个具体目标是确定电和药物神经调节相结合的疗效。第二个具体目标是开发有效的、非侵入性的神经调节方法。该项目的创新之处在于其组合方法，利用药理和电神经调节来靶向多个神经递质/受体，以治疗多因素疾病-OAB。本项目的成功可以为OAB创造几种新的治疗策略，具有疗效高、不良反应少、侵袭性小、易于管理、易为更多患者接受的特点，尤其适用于不能耐受药物治疗或侵入性手术治疗的老年和儿童患者。我们的研究将极大地造福数百万患有OAB的美国人。 公共卫生相关性：膀胱过度活跃(OAB)对生活质量的影响是心理的、社会的和深刻的。目前，成功治疗OAB仍然是临床医生面临的一个治疗挑战。我们的项目可以为OAB创造几种新的治疗策略，具有疗效高、不良反应少、侵袭性小、易于管理、可被更多患者(老年人和儿童)接受的特点，并显著造福于数百万患有OAB的美国人。

DESCRIPTION (provided by applicant): Overactive bladder (OAB) is defined by the International Continence Society as a syndrome characterized by urgency with or without urge incontinence, usually with frequency and nocturia. About 33.3 million adults suffer from OAB in United States. The overall prevalence of OAB was 16.9% in women and 16.2% in men. The impact of OAB on quality of life is psychological, social, and profound. Antimuscarinic drugs are the first-line pharmacotherapy. However, many OAB patients withdraw from antimuscarinic treatment within 6-12 months due to its moderate efficacy and significant adverse effects such as dry mouth, constipation, headache, and blurred vision. Sacral neuromodulation is another treatment option, which is only offered to OAB patients after pharmacotherapy failed. However, the clinical benefit of sacral neuromodulation is significantly limited by its invasiveness, cost, and the requirement for well-trained surgeons. Currently it remains as a therapeutic challenge for clinicians to successfully treat OAB. The goal of this grant application is to develop new strategies to meet this therapeutic challenge. We hypothesize that combination of electrical and pharmacological neuromodulation can significantly improve the efficacy of current treatments for OAB, and create new, effective, non-invasive treatments acceptable for more patients. The first specific aim is to determine the efficacy of combined electrical and pharmacological neuromodulation. The second specific aim is to develop effective, non-invasive neuromodulation methods. The innovation of this project lies in its combinatorial approach that utilizes both pharmacological and electrical neuromodulation to target multiple neurotransmitters/receptors in order to treat the multifactorial disease - OAB. The success of our project could create several new treatment strategies for OAB with high efficacy, less adverse effect, less invasiveness, easy management, and acceptable for more patients, especially for the elderly and children patients who can not tolerate the adverse effects of pharmacotherapy or invasive surgery of sacral neuromodulation. Our studies will significantly benefit millions of Americans suffering from OAB. PUBLIC HEALTH RELEVANCE: The impact of overactive bladder (OAB) on quality of life is psychological, social, and profound. Currently it remains as a therapeutic challenge for clinicians to successfully treat OAB. Our project could create several new treatment strategies for OAB with high efficacy, less adverse effect, less invasiveness, easy management, acceptable for more patients (elderly and children), and significantly benefit millions of Americans suffering from OAB.