Stress urinary incontinence (SUI) can result from a combinatorial neuromuscular injury to the pudendal nerve and the muscle it innervates, the external urethral sphincter (EUS), compounded by the biochemical effects of aging. The mechanisms of SUI development include incomplete pudendal nerve regeneration and EUS sphincter repair from the maternal polytrauma of childbirth as well as biochemical changes with aging. Surgery and injectable bulking agents are used to treat SUI, but there is currently no effective therapeutic for this indication. Theratome Bio, Inc. is developing a next-generation regenerative medicine that is based on factors secreted by adult adipose-derived stem cells. This therapeutic, Thera-101, has demonstrated neurogenic activity in vitro and in vivo and functional improvement in preclinical models of ischemic brain injury, stroke, neurodegenerative disease, and limb ischemia. Due to its regenerative effects and prior observation that rat stem cell secretome has demonstrated efficacy in animal models of SUI we hypothesize that Thera-101 or secretome product prepared by similar clinically compliant methods will be as effective as rat stem cell secretome in treating SUI in the proposed preclinical model. Successful completion of this project will result in selection of a candidate secretome preparation that can be rapidly progressed to clinical trials in SUI.
Public Health Relevance Statement: Narrative Stress Urinary Incontinence (SUI) is a significant medical issue with profound social implications. SUI prevalence increases with age and with multiple vaginal deliveries in female population due to combined effects of aging and injury to neuromuscular tissues of the urogenital tract and pelvic floor. There is currently no therapeutic that is effective in treatment SUI. We have previously demonstrated that a regenerative therapy comprised of rat stem cell secretome is efficacious in an animal model of SUI. We propose in this application to bridge from this rodent preparation to a clinically compliant, human stem cell secretome therapy for rapid translation to clinical trials.
Project Terms: Address; Adipose tissue; Adult; Affect; Age; age effect; Aging; angiogenesis; Animal Model; base; Biochemical; Biological Assay; Biological Availability; Biological Products; Bone Marrow; cell bank; Cell Culture Techniques; Cell Therapy; Cells; Child; Childbirth; Clinical; Clinical Treatment; Clinical trial protocol document; Clinical Trials; combinatorial; Comorbidity; Complex; Consultations; Coughing; cytokine; Data; Development; Diabetes Mellitus; Disease; Dose; Effectiveness; Engraftment; Exertion; Exhibits; experimental study; Extravasation; Female; Formulation; functional improvement; Histology; Human; human stem cells; immunoregulation; implantation; In Vitro; in vitro activity; in vivo; Incidence; Injectable; Injury; intraperitoneal; Ischemia; Ischemic Brain Injury; Legal patent; Limb structure; manufacturing process; Mediating; Medical; meetings; Mesenchymal Stem Cells; Methods; minimally invasive; Modeling; Muscle; myogenesis; Nerve; Nerve Regeneration; nerve supply; Neurodegenerative Disorders; neurogenesis; neuromuscular; next generation; Obesity; off-patent; Operative Surgical Procedures; Outcome; Outpatients; Pelvic Floor Disorders; Pelvic floor structure; Pelvis; Phase; Population; Postmenopause; Pre-Clinical Model; Preparation; pressure; Prevalence; Process; Production; Property; Rattus; Recovery; regenerative; Regenerative Medicine; regenerative therapy; Regimen; reinnervation; repaired; Research; Rodent; Rodent Model; Safety; scale up; Small Business Technology Transfer Research; Sneezing; social implication; sound; Sphincter; standard of care; Stem cells; Stress Urinary Incontinence; Stroke; success; Testing; Therapeutic; therapeutic development; Therapeutic Effect; Tissues; translational study; Translations; Treatment Efficacy; Urethral sphincter; Urinary Incontinence; Urine; urogenital tract; Vaginal delivery procedure; Woman
