# Neurokinin-2 receptor-induced micturition and defecation in aged diabetic rats

> **NIH NIH R43** · DIGNIFY THERAPEUTICS, LLC · 2020 · $295,650

## Abstract

ABSTRACT
Underactive bladder (UAB) or anorectal defecation dysfunction are conditions in which the
bladder or rectum, respectively, do not completely empty because bladder or colorectal smooth
muscle contractions are too weak or unsustained and cannot overcome the resistance of the
urethral or anal sphincters, respectively. This results in bladder symptoms of urinary frequency,
urgency, incontinence, and urinary retention (which can potentially lead to renal dysfunction)
and bowel symptoms of constipation (which can lead to fecal impaction). UAB and anorectal-
related constipation are prominent in elderly and diabetic patients and especially severe in
elderly, diabetic patients. Dignify Therapeutics has been developing selective neurokinin-2
receptor (NK2R) agonists as “on-demand, rapid-onset, short-duration, drug-induced, voiding
therapy” for individuals with spinal cord injury and are also exploring their utility as treatment for
UAB and anorectal-related constipation in elderly diabetic patients. We have previously
demonstrated that NK2R agonists exhibit efficacy and safety in aged Fischer/Brown Norway
(F/BN) rats that is comparable to that in young adult animals. The current application extends
those studies to include aged, diabetic F/BN rats. The Specific Aims will use cystometric and
colorectal manometric techniques to determine if a selective NK2R agonist, DTI-117, produces
bladder and colorectal contractions in young and aged F/BN rats that have been treated with
streptozotocin (STZ) to produce diabetic bladder and colorectal dysfunction. Efficacy and safety
of DTI-117 will be compared in diabetic vs non-diabetic adult and aged rats. Cardiovascular
and respiratory effects of DTI-117 will be measured for the initial assessment of safety. Positive
results from the proposed project will validate the use of DTI-117 for treatment of aged, diabetic
UAB and anorectal-related constipation and provide the rationale for Dignify Therapeutics to
include elderly, diabetic patients in the clinical development program for DTI-117. This therapy
would greatly improve the daily routine of individuals with UAB and anorectal-related
constipation by reducing UTIs and associated health risks, decreasing healthcare costs, and
improving quality of life for elderly, diabetic patients.

## Key facts

- **NIH application ID:** 10080006
- **Project number:** 1R43DK125131-01A1
- **Recipient organization:** DIGNIFY THERAPEUTICS, LLC
- **Principal Investigator:** LESLEY MARSON
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $295,650
- **Award type:** 1
- **Project period:** 2020-09-21 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080006

## Citation

> US National Institutes of Health, RePORTER application 10080006, Neurokinin-2 receptor-induced micturition and defecation in aged diabetic rats (1R43DK125131-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10080006. Licensed CC0.

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