A decellularized porcine placenta matrix hydrogel for management of radiation-induced proctitis

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PROJECT SUMMARY Radiation therapy is a widely used treatment modality for pelvic malignancies such as prostate and cervical cancer; however, the high doses needed to confer therapeutic benefit often inflict significant damage on the normal issue in and surrounding the radiation field. The most frequent complication of pelvic radiation is proctitis, which nearly all patients experience acutely and many experience chronically in the months and years following cessation of therapy. In its most severe form, radiation induced proctitis leads to compromise of the blood supply to the rectal wall, which results in full thickness ischemia, stenosis, and fecal obstruction. Treatment strategies follow a pragmatic approach of first-line anti-inflammatories alone or in combination with a steroid, followed by cytoprotective agents like sucralfate. While these strategies are associated with symptom relief in some cases, data are not strong enough to support widespread use, leaving clinicians without legitimate evidence-based therapies to recommend. BrioPryme Biologics, Inc. has developed a single patient/multiuse biologic device (sterile powder) derived from DeCellularized porcine placenta extracellular Matrix (DCM) that can be rehydrated at point of use and delivered directly to the anorectum as an enema irrigation. BrioPryme’s DCM hydrogel device forms a protective layer and adheres onto the mucosal membrane to relieve temporary irritations and provides a moist environment and a 3D scaffold to optimize wound healing. The DCM hydrogel device can be fully absorbed within 1-3 hours. It has demonstrated potential to reduce fibrotic progression when applied at time of injury, and is safe, non-toxic, and neutral towards tumor growth. Case studies in cancer patients that recently received repeated sessions of pelvic radiotherapy reported significant improvements in proctitis symptoms and quality of life following self-administration of DCM. Based on these promising studies, BrioPryme has partnered with University of California Davis Department of Radiation Oncology to define the molecular features of DCM- mediated repair (AIM 1) and evaluate the efficacy of DCM to alleviate radiation injury and stenosis in a mouse model of radiation-induced proctitis (AIM 2). Successful completion of the proposed work will establish efficacy of DCM for the management of skin and mucosal membrane toxicity resulting from radiotherapy and pave the way for formal clinical evaluation of this claim in cancer patients.