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

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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.