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

用于治疗放射性直肠炎的脱细胞猪胎盘基质水凝胶

基本信息

批准号：
10599727
负责人：
Jian Jian Li
金额：
$ 40万
依托单位：
BRIOPRYME BIOLOGICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10599727
关键词：
3-Dimensional Acute Adhesions Amifostine Amino Acids Animals Anti-Inflammatory Agents Antibiotics Antioxidants Area Biological Biological Factors Biological Products California Cancer Patient Cancer Survivor Case Study Cell Adhesion Cells Chronic Clinical Collagen Colon Colorectal Complication Conformal Radiotherapy Cytoprotective Agent Cytoskeleton DNA Repair Data Devices Dose Dose Limiting Dryness Elastin Electromagnetic Energy Environment Epithelial Cells Epithelium Euthanasia Exhibits Exposure to Extracellular Matrix Family suidae Fibrosis Film Glycosaminoglycans Growth Factor Histologic Hour Hydration status Hydrogels Hyperbaric Oxygenation Immune Inflammation Inflammatory Injury Intestinal Obstruction Intestines Irrigation Ischemia Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of prostate Measures Mediating Medical Membrane Modality Modeling Molecular Monitor Morphology Motivation Mucous Membrane Mus Normal Cell Normal tissue morphology Obstruction Organoids Oryctolagus cuniculus Pathologic Patients Pelvis Peptides Phase Placenta Powder dose form Proctitis Proliferating Proteins Quality of life RNA Radiation Radiation Dose Unit Radiation Injuries Radiation Oncologist Radiation Oncology Radiation Protection Radiation therapy Recommendation Rectal Cancer Rectum Regimen Reporting Resistance Saline Secondary to Self Administration Skin Small Business Technology Transfer Research Stenosis Sterility Steroids Structure Sulfasalazine Symptoms Syndrome Tail Testing Therapeutic Thick Thinness Time Tissues Toxic effect Transcript Universities Vascular blood supply Work absorption acute symptom chemokine cohort comparison control cytokine effective therapy efficacy evaluation enema administration evidence base experience immunoreaction improved in vivo innovation intestinal epithelium intestinal injury irritation matrigel mouse model neoplastic cell p53-binding protein 1 persistent symptom preservation prevent primary endpoint prophylactic radiation mitigation radiation response radiation-induced injury radioprotected rectal reduce symptoms repaired research clinical testing scaffold stem cell proliferation stem cell self renewal stem cells symptomatic improvement treatment strategy tumor growth wound healing

项目摘要

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.

项目概要放射治疗是治疗前列腺癌和宫颈癌等盆腔恶性肿瘤的一种广泛使用的治疗方式癌症；然而，提供治疗效果所需的高剂量往往会对身体造成重大损害。放射野及其周围的正常问题盆腔放射最常见的并发症是直肠炎，几乎所有患者都会急性经历这种情况，而许多患者在接下来的数月和数年内会长期经历这种情况在最严重的情况下，放射诱发的直肠炎会导致血液供应受损。直肠壁，导致全层缺血、狭窄和粪便阻塞。遵循实用的方法，单独使用一线抗炎药或与类固醇联合使用，然后虽然这些策略在某些情况下与症状缓解有关，但数据不够强大，不足以支持广泛使用，使忠诚者没有合法的证据基础 BrioPryme Biologics, Inc. 开发了一种单一患者/多用途生物设备。（无菌粉末）源自可再水化的脱细胞猪胎盘细胞外基质 (DCM) 在使用时作为 BrioPryme 的 DCM 水凝胶装置直接输送到肛门直肠。形成保护层并粘附在粘膜上，以缓解暂时的刺激并提供湿润的环境和 3D 支架可以充分优化伤口愈合。它已被证明在 1-3 小时内被吸收，可减少纤维化进展。最近在癌症患者中进行的案例研究表明，该药物对肿瘤生长无伤害，并且安全、无毒且对肿瘤生长呈中性。接受重复的盆腔放射治疗报告直肠炎症状有显着改善基于这些有前景的研究，BrioPryme 开展了合作。与加州大学戴维斯分校放射肿瘤学系合作定义 DCM 的分子特征- 介导修复 (AIM 1) 并评估 DCM 减轻小鼠放射损伤和狭窄的功效放射性直肠炎模型（AIM 2）的成功完成将确定疗效。 DCM 用于治疗放疗引起的皮肤和粘膜毒性，并为治疗放疗引起的皮肤和粘膜毒性奠定基础。在癌症患者中正式临床评估这一主张的方法。