Research Project
9138560
? 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 individuals. 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 for urinary retention consists of cholinergic agonists, which have minimal efficacy and severe side effects. Consequently, many people with SCI catheterize multiple times daily to empty their bladder. 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 individuals, and a significant reduction in individual and community health care costs. Dignify Therapeutics is a drug development company focused on advancing novel drug therapies for patients with SCI, multiple sclerosis and similar diseases that result in voidin dysfunction. By combining novel pharmaceuticals with novel drug delivery technology, Dignify Therapeutics hopes to redefine treatment of voiding disorders and restore the dignity of voluntary excretory function in a way that mimics normal micturition. Dignify Therapeutics' lead compound, DTI-100, is being developed as the first on-demand pharmaceutical to induce bladder voiding without catheterization. Phase II studies are proposed in a translational rat model of SCI to establish the efficacy of DTI-100. Chronic SCI often results in detrusor- sphincter dyssynergia (DSD) in which the external urethral sphincter fails to properly relax during micturition, resulting in impaired voiding efficiency. Proposed studies will examine the effects of DTI-100 on bladder function in a rat SCI model with and without urethral smooth and/or striated muscle activity. These studies are essential to confirm the utility of DTI-100 in treating chronic SCI-induced voiding dysfunction in humans. To enable submission of an Investigational New Drug (IND) application and subsequent use of DTI-100 in humans, FDA-regulated drug safety and toxicology studies are required. Phase II studies are proposed to establish a toxicity and safety profile for DTI-100 that is acceptable for IND submission. Studies including repeated dose toxicology, cardiovascular, and pulmonary safety studies in two animal species will be performed to identify an acceptable dose range for human administration. Manufacture of DTI-100 drug product for use in clinical studies will also be completed. Successful completion of these studies will enable a clinical study of the safety, tolerability and pharmacodynamics of DTI-100 in humans and suggest therapeutic approaches to reduce urethral resistance in patients with high resistance (e.g. DSD).
