New Strategies to Treat Overactive Bladder

描述（由申请人提供）：膀胱过度活动症（OAB）由国际尿失禁协会定义为一种以尿急伴或不伴急迫性尿失禁为特征的综合征，通常伴有尿频和尿失禁。在美国，大约有3330万成年人患有OAB。OAB的总体患病率在女性中为16.9%，在男性中为16.2%。OAB对生活质量的影响是心理的、社会的和深刻的。抗毒蕈碱药物是一线药物治疗。然而，许多OAB患者在6-12个月内退出抗毒蕈碱治疗，这是由于其中等疗效和显著的不良反应，如口干、便秘、头痛和视力模糊。骶神经调节是另一种治疗选择，仅在药物治疗失败后提供给OAB患者。然而，骶神经调节的临床受益受到其侵入性、成本和对训练有素的外科医生的要求的显著限制。目前，成功治疗OAB仍然是临床医生的治疗挑战。这项资助申请的目标是开发新的策略来应对这一治疗挑战。我们假设电和药物神经调节的组合可以显著提高目前治疗OAB的疗效，并创造出更多患者可接受的新的、有效的、非侵入性的治疗方法。第一个具体目标是确定组合的电和药理学神经调节的功效。第二个具体目标是开发有效的非侵入性神经调节方法。该项目的创新在于其组合方法，该方法利用药理学和电神经调节来靶向多种神经递质/受体，以治疗多因素疾病- OAB。本课题的成功为OAB的治疗开辟了新的思路，具有疗效高、不良反应少、创伤小、易于管理、可为更多患者接受等优点，尤其适用于不能耐受骶神经调节药物治疗或有创手术不良反应的老年和儿童患者。我们的研究将使数百万患有OAB的美国人受益匪浅。 公共卫生相关性：膀胱过度活动症（OAB）对生活质量的影响是心理，社会和深刻的。目前，成功治疗OAB仍然是临床医生的治疗挑战。我们的项目可以为OAB创造几种新的治疗策略，这些策略具有高疗效，不良反应少，侵入性小，易于管理，可为更多患者（老年人和儿童）接受，并使数百万患有OAB的美国人受益。

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.