Examination of a novel therapy to induce voiding after spinal cord injury

脊髓损伤后诱导排尿的新疗法的研究

• 批准号: 8969641
• 负责人: LESLEY MARSON
• 金额: $ 35万
• 依托单位: DIGNIFY THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8969641
• 关键词: Adult; Adverse effects; Adverse event; Agonist; Anesthesia procedures; Animal Behavior; Animal Model; Animals; Behavior; Behavioral; Bladder; Bladder Control; Bladder Tissue; Cannulas; Catheterization; Catheters; Cholinergic Agonists; Chronic; Climacteric; Clinical; Clinical Trials; Collagen; Community Healthcare; Conscious; Data; Development; Disease; Dose; Drug Delivery Systems; Drug Kinetics; Effectiveness; Elastin; Excretory function; Exhibits; Experimental Designs; Female; Functional disorder; Goals; Grant; Health; Health Care Costs; Health Status; Histology; Hospitalization; Hour; Implant; Incidence; Individual; Intestines; Intravenous; Lead; Life; Measurement; Mental Depression; Mental Health; Modeling; Morphology; Multiple Sclerosis; Paraplegia; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pharmacotherapy; Plasma; Publishing; Quality of life; Rattus; Recovery; Research Design; Saline; Sampling; Sepsis; Serious Adverse Event; Smooth Muscle; Sphincter; Spinal; Spinal cord injury; Spinal cord injury patients; Staining method; Stains; Substance K Receptor; Technology; Testing; Therapeutic; Time; Urethra; Urethral sphincter; Urinary Retention; Urinary tract infection; Urination; Urine; animal data; attenuation; awake; base; design; drug development; improved; in vivo; instrument; intravenous administration; male; men' s group; nervous system disorder; novel; physical conditioning; pre-clinical; preclinical efficacy; pressure; prevent; programs; public health relevance; research study; response; success; treatment duration

 DESCRIPTION (provided by applicant): Loss of voluntary control over bladder and bowel function as a result of spinal cord injury (SCI) has profound impact on the mental and physical health status and quality of life of patients. It is estimated that 270,000 people in the USA have SCI ((https://www.nscisc.uab.edu/PublicDocuments/fact_figures_docs/.pdf). Urinary retention as a result of SCI is irreversible and can be life threatening. The only available pharmacotherapy consists of cholinergic agonists, which have minimal efficacy and severe side effects. Consequently, patients catheterize multiple times daily to empty their bladder. Catheter use is associated with increased incidence of health problems, predominately repeated urinary tract infections, sepsis, isolation, depression and hospitalization. An "on demand", safe and effective pharmaceutical alternative to catheterization would be a life-changing improvement in the daily routine of bladder management for SCI patients, and would significantly reduce individual and community health care costs. Dignify Therapeutics is a drug development company that aims to restore voluntary control of bladder function for patients with SCI, multiple sclerosis and similar neurological diseases that result in voiding dysfunction. By combining novel pharmaceutical, smooth muscle prokinetics with novel drug delivery technology, Dignify Therapeutics hopes to redefine treatment of voiding disorders and restore the dignity of voluntary excretory function for these patients in a way that mimics normal voiding. This application examines our lead program, DTI-100, a smooth muscle prokinetic agent that rapidly induces micturition without noticeable adverse behavioral effects during intravenous administration to rats. Studies are proposed in chronic male and female SCI rats to provide in vivo proof of concept (POC) data, provide intravenous (i.v.) dose ranges, and voiding efficacy of DTI-100 and to examine the feasibility of repeated dosing to determine the extent of tolerance to compound administration. The successful completion of the proposed studies will provide efficacy and pharmacodynamics data in a translational model of chronic SCI to support the clinical development of DTI-100.

 描述（由申请人提供）：脊髓损伤（SCI）导致的膀胱和肠功能自主控制丧失对患者的身心健康状况和生活质量产生深远影响。据估计，美国有270，000人患有SCI（https：//www.nscisc.uab.edu/PublicDocuments/fact_figures_docs/.pdf）。SCI导致的尿潴留是不可逆的，可能危及生命。唯一可用的药物治疗包括胆碱能激动剂，其具有最小的功效和严重的副作用。因此，患者每天多次导尿以排空膀胱。导尿管的使用与健康问题的发生率增加有关，主要是反复尿路感染、败血症、隔离、抑郁和住院。“按需”，安全和有效的药物替代导管将是一个改变生活的改善日常膀胱管理的SCI患者，并将显着降低个人和社区的医疗保健成本。Dignify Therapeutics是一家药物开发公司，旨在为SCI，多发性硬化症和类似疾病的患者恢复膀胱功能的自主控制。 导致排尿功能障碍的神经系统疾病。通过将新型药物、平滑肌促动力剂与新型药物递送技术相结合，Dignify Therapeutics希望重新定义排尿障碍的治疗，并恢复自主排泄功能的尊严， 这些病人的排尿方式就像正常排尿一样。该应用程序检查了我们的铅程序，DTI-100，一种平滑肌促动力剂，可快速诱导排尿，在大鼠静脉给药期间无明显的不良行为影响。提出在慢性雄性和雌性SCI大鼠中进行研究以提供体内概念验证（POC）数据，提供静脉内（i. v.）剂量范围和DTI-100的排尿功效，并检查重复给药的可行性以确定对化合物给药的耐受程度。拟议研究的成功完成将提供慢性SCI转化模型中的疗效和药效学数据，以支持DTI-100的临床开发。