Small molecule enhancers of detrusor contraction discovered using a functional cell contractility screen as therapeutic candidates for underactive bladder

Underactive bladder (UAB) / detrusor underactivity (DU), is a chronic disorder arising from impaired contractile function of the bladder in its strength and/or duration, causing prolonged bladder voiding or inability to achieve complete voiding of the bladder at normal time scales. Without treatment, increased urinary retention and back-up will lead to severe and irreversible bladder damage and chronic kidney disease. No available oral medication used in the UAB is completely effective and catherization is often the standard recommendation for managing urinary retention resulting from UAB, even in pediatric patients with idiopathic UAB. This requires the patient either to carry an indwelling catheter and external collection device or more commonly, to self-catheterize four and six times daily, a involving manually guiding a catheter through one’s urethra to the bladder. Forcyte performed the first ever high-throughput screen on bladder cell contractility of 11500 small molecules, identifying two promising hit clusters. In addition to the parent grant aims around phenotypic small molecule discovery, this ADMIN SUPPLEMENT will train a candidate from an underrepresented group in both research and commercialization tasks at Forcyte. In particular, the candidate will aide the company’s commercial expansion into target discovery by working with an expert Sr. Scientist to develop CRISPR techniques for “gain-of-contractile-function” screening.