BioSphincter to Treat Fecal Incontinence. Phase 1/2 Clinical Trial. SBIR Phase IIB

Project Summary/Abstract:Fecal incontinence (FI), the involuntary soiling of various amounts of liquid and solid stool, is often devastating from a social, psychological, and hygiene perspective. Men and women suffer from FI equally with a range of 2 - 6% in people aged 20 - 30 years. The prevalence increases to over 15% in people older than 70 years1. FI may result from an isolated or combined loss of smooth muscle function (IAS), skeletal muscle function (EAS), anorectal sensory mechanisms or neural control.Treatment of FI is initially conservative with attempts to bulk the stool, adjust or stop drugs that cause either diarrhea or constipation, and biofeedback2,3. While these conservative measures may improve the severity of FI, additional therapies are needed for total symptom management. Injection of various biomaterials to augment the internal anal sphincter has also been attempted4, but results have been variable and of limited duration when effective. In the past, surgical attempts with anterior/posterior surgical repair have been tried such as graciloplasty and sacral nerve stimulation5,6, but long-term results have been disappointing6.There is a critical need for new therapies to address FI, particularly for patients who have severe passive incontinence and low IAS pressure. Regenerative medicine methods, wherein a new IAS BioSphincter™ is bioengineered from the patientandapos;s own cells and implanted to restore the structure and function of the IAS and treat FI, represents a rational and novel approach to this debilitating disease. Regeneration and implantation of the IAS “BioSphincter™” can restore physiological function of the IAS, improve or resolve FI, and improve quality of life. Following implantation in rodents, the engineered sphincters became vascularized and maintained their phenotype and functionality7,8. Further in our large animal studies, the developed IAS BioSphincter™ were validated to treat the FI and successfully restored anorectal functionality in rabbit9,10 and non-human primates11. The IAS BioSphincter™ was developed in GLP condition further scaled up for manufacturing following GMP guidelines and put together for FDA application. According to NIDDK, NIH, one out of three people report to health care providers owing to fecal incontinence, therefore, regeneration and implantation of the IAS “Biosphincter™” will benefit a large socially distressed segment of population via restoration of physiological function of the IAS, resolve FI, and improving quality of life.The primary objectives of the phase I clinical trial study are to: 1) determine the safety of the implanted bioengineered IAS in patients with severe FI and 2) to analyse the data in order to assess the initial efficacy potentials of the implanted IAS in decreasing the number of episodes of incontinence in patients with severe FI. This new innovative approach will provide the patients with a better quality of life, and reinstate continence, by providing an additive functional intrinsically innervated IAS bioengineered from their own cells.Project Narrative:This is a prospective study of immediate and long-term safety and potential efficacy of an implanted IAS BioSphincter™ to treat patients with severe fecal incontinence who failed standard therapies. This new innovative approach will provide the patients with a better quality of life, and reinstate continence, by providing an additive functional intrinsically innervated IAS bioengineered from their own cells.