Dignify Therapeutics LLC — Department of Health and Human Services STTR Phase I: 102

Description

DESCRIPTION provided by applicant Neurological conditions such as multiple sclerosis Parkinsonandapos s disease dementia spina bifida diabetes stroke and spinal cord injury SCI can result in loss of voluntary control over bladder and bowel function often producing both incontinence and retention of urine and stools in the same patient This has a profound impact on the mental and physical health status and quality of life of patients as well as a large impact on health care costs For example urinary retention is generally 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 themselves multiple times daily to empty their bladder Catheter use is associated with increased incidence of urinary tract infections sepsis isolation depression and hospitalization An andapos on demandandapos saf and effective pharmaceutical alternative to catheterization would be a life changing improvement in the daily routine of bladder management for patients not to mention a significant reduction in individual and community health care costs Similarly andapos on demandandapos bowel control would provide substantial improvement in andapos quality of lifeandapos for people with neurogenic bowel Dignify Therapeutics is developing an andapos on demand rapid onset short duration drug induced voidingandapos therapy using an analogue of neurokinin A Lys MeLeu Nle NKA aka DTI DTI is a potent and selective agonist of the NK receptor which induces powerful contractions of the human bladder and rectum in vitro and provides highly promising in vivo efficacy safety and pharmacodynamic PD profiles in various dog and rat models spinal intact SCI and diabetes following IV administration Presently the overarching objective of its development program is to discover a formulation that is more convenient for people with neurological conditions but maintains the therapeutic benefit of the IV formulation The specific aims of the current Phase I application are to examine the suitability of an intranasal IN formulation and an orally dissolving film ODF formulation Based on previous work with systemic delivery of similar peptides from each of the formulations it is anticipated that either may provide a stable dosage that provides rapid release systemic absorption and PD activity The specific aims of this Phase I application are to compare stability and release rates of each formulation containing various media and to compare the in vivo activity of the most optimized formulations using a simple but clinically relevant anesthetized acute spinal rat cystometry model If positive results are obtained detailed pharmacokinetic studies and testing in additional species and neuropathological models are proposed for Phase II studies PUBLIC HEALTH RELEVANCE The ultimate aim of this project is to provide patients with neurogenic bladder retention a pharmaceutical alternative to multiple daily catheterization of their bladder to void urine Passage of a catheter into the urethra and bladder can be discomforting and stigmatizing and is associated with urinary tract infections and various other complications Success of our project which involves developing intranasal and orally dissolving film formulations will restore patientsandapos dignity and improve their daily quality of lif and health as well as reducing individual and community health care costs This grant will provide important information on the feasibility and stability of alternative formulations with efficacy measures in a preclinical model of micturition for a novel drug to produce voiding