A Novel Probiotic Platform to Treat Necrotizing Enterocolitis

治疗坏死性小肠结肠炎的新型益生菌平台

• 批准号: 9344825
• 负责人: GAIL E BESNER
• 金额: $ 33.14万
• 依托单位: MONON BIOVENTURES, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9344825
• 关键词: Affect; Animal Model; Bacteria; Biological Markers; Cause of Death; Clinical; Complex; Data; Development; Disease; Dose; Effectiveness; Exhibits; Family suidae; Formulation; Gastrointestinal Diseases; Genotype; Goals; Growth; Health; Human; Infant; Intestines; Investigational Drugs; Lactobacillus reuteri; Left; Licensing; Liver diseases; Maximum Tolerated Dose; Methods; Microbial Biofilms; Microspheres; Modeling; Morbidity - disease rate; Necrotizing Enterocolitis; Outcome; Patients; Pediatric Hospitals; Performance; Phase; Phenotype; Positioning Attribute; Premature Infant; Preventive; Probiotics; Production; Rattus; Research; Research Institute; Safety; Short Bowel Syndrome; Small Business Technology Transfer Research; Surrogate Endpoint; System; Technology; Time; Toxic effect; Work; commercialization; comparative efficacy; cost; dosage; evidence base; experience; innovation; mortality; novel; novel strategies; point of care; pre-clinical; prevent; prototype; reconstitution; response; scale up

PROJECT SUMMARY Probiotics hold enormous potential for promoting human health and treating disease. One major hurdle to many probiotic products is their lack of persistence in the gut. Monon Bioventures (MBV) and their research partners at the Research Institute at Nationwide Children's Hospital (RINCH) are developing a novel, enhanced, tunable technology called ProNextTM, that allows for a persistent probiotic benefit from just a single dose. The combination of ProNextTM and the probiotic Lactobacillus reuteri will create the first commercial- grade probiotic platform product “ProTect”. This STTR proposal focuses on the development of ProTect as the first single dose treatment that protects premature infants from necrotizing enterocolitis (NEC). Necrotizing enterocolitis (NEC) is a devastating disease affecting premature infants. Approximately 10% of infants born under 1500 g will develop the disease, and mortality for affected infants is 20-30%. Despite decades of research, the morbidity and mortality of the disease remain generally unchanged, and treatment and preventive approaches for NEC remain suboptimal. NEC is still the leading cause of death from gastrointestinal disease in premature infants, with an associated cost of $500 million to $1 billion annually for treatment in the US alone. Novel approaches for the treatment of patients with NEC are critically needed. In Phase I of this STTR, MBV and RINCH will accomplish three specific aims necessary to move towards commercialization: Aim (1) Produce a functional, scalable, stable prototype of the ProNext™ Probiotic platform (ProTect) that can be productized; Aim (2) Determine the efficacy of ProTect compared to the current probiotic formulation for protection of the intestines from NEC. Aim (3) Determine the optimal dose and establish the initial safety of ProTect for protection of the intestines from NEC. This Phase I STTR project will allow MBV and RINCH to collect the pivotal data needed to scale up to a large animal model in Phase II, and to license the technology to a commercial partner in Phase III for commercialization. The product proposed here will be the first effective solution to this unmet clinical need.

项目摘要 益生菌在促进人类健康和治疗疾病方面具有巨大的潜力。一个主要的障碍， 许多益生菌产品的缺点是它们在肠道中缺乏持久性。莫农生物公司及其研究 全国儿童医院研究所（RINCH）的合作伙伴正在开发一种新的， 增强的可调技术ProNextTM，仅从一种单一的益生菌中获得持久的益生菌益处， 次给药结束ProNextTM和益生菌罗伊氏乳杆菌的结合将创造第一个商业化的- 级益生菌平台产品“ProTect”。该STTR提案侧重于开发ProTect， 第一次单剂量治疗，保护早产儿坏死性小肠结肠炎（NEC）。 坏死性小肠结肠炎（NEC）是一种影响早产儿的毁灭性疾病。约10%的 出生时体重在1500克以下的婴儿会患上这种疾病，受影响婴儿的死亡率为20- 30%。尽管 经过几十年的研究，该病的发病率和死亡率基本保持不变， NEC的预防方法仍然不理想。NEC仍然是导致死亡的主要原因。 早产儿胃肠道疾病，每年的相关费用为5亿至10亿美元， 仅在美国治疗。迫切需要治疗NEC患者的新方法。 在本STTR的第一阶段，MBV和RINCH将实现三个必要的具体目标， 商业化：目标（1）生产ProNext™益生菌平台的功能性、可扩展、稳定的原型 目的（2）确定ProTect与当前益生菌相比的功效 用于保护肠免受NEC的制剂。目的（3）确定最佳剂量，建立 保护肠免受NEC的ProTect的初始安全性。该一期STTR项目将允许MBV和 RINCH将收集II期扩大到大型动物模型所需的关键数据，并许可 在第三阶段将技术提供给商业伙伴进行商业化。这里提出的产品将是 第一个有效解决这一未满足的临床需求。