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: 9146762
• 负责人: LESLEY MARSON
• 金额: $ 35.1万
• 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/9146762
• 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; novel therapeutics; 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(申请人提供)：脊髓损伤(SCI)导致的膀胱和肠道功能自主控制的丧失对患者的身心健康状况和生活质量有深远的影响。据估计，美国有270,000人患有SCI((https://www.nscisc.uab.edu/PublicDocuments/fact_figures_docs/.pdf).脊髓损伤导致的尿潴留是不可逆转的，可能危及生命。唯一可用的药物治疗方法是胆碱能激动剂，其疗效极低，副作用严重。因此，患者每天都要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。一种“按需”、安全有效的药物替代导尿术将改变脊髓损伤患者的日常膀胱管理，并将显著降低个人和社区的医疗保健成本。Treatify Treateutics是一家药物开发公司，旨在为脊髓损伤、多发性硬化症和类似的导致排尿功能障碍的神经疾病患者恢复对膀胱功能的自愿控制。通过将新药物、平滑肌促动力作用与新的药物输送技术相结合，Diguify Treeutics希望重新定义排尿障碍的治疗，并以一种模拟正常排尿的方式恢复这些患者自愿排泄功能的尊严。此应用程序检查我们的先导程序DTI-100，这是一种平滑肌促动力药，在静脉给药期间快速诱导排尿，没有明显的不良行为影响。建议在慢性脊髓损伤雄性和雌性大鼠中进行研究，以提供体内概念验证(POC)数据，提供静脉(IV)。目的是研究DTI-100的剂量范围和排尿效果，并检查重复给药的可行性，以确定对复合给药的耐受程度。拟议研究的成功完成将为慢性脊髓损伤的翻译模型提供疗效和药效学数据，以支持DTI-100的临床开发。