A Novel Probiotic Platform to Treat Necrotizing Enterocolitis

项目总结 益生菌在促进人类健康和治疗疾病方面具有巨大的潜力。实现以下目标的一个主要障碍 许多益生菌产品是它们在肠道中缺乏持久性。Monon BioVenture(MBV)及其研究 国立儿童医院(RINCH)研究所的合作伙伴正在开发一种新的， 名为ProNextTM的增强型可调技术，允许仅从单个 剂量。ProNextTM和益生菌reuri的结合将创造第一个商业- 级益生菌平台产品“保”。这份STTR提案侧重于将保护作为 第一个保护早产儿免受坏死性小肠结肠炎(NEC)影响的单剂治疗。 坏死性小肠结肠炎(NEC)是影响早产儿的一种破坏性疾病。约10%的 出生在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大体保持不变，而治疗 而预防NEC的方法仍然不是最优的。NEC仍然是导致死亡的主要原因 早产儿的胃肠道疾病，每年的相关成本为5亿至10亿美元 仅在美国接受治疗。迫切需要治疗NEC患者的新方法。 在这个STTR的第一阶段，MBV和RINCH将实现三个必要的具体目标 商业化：AIM(1)生产ProNext™益生菌平台的功能、可扩展、稳定的原型 (PROTECT)可生产的；目的(2)确定PROTECT与当前益生菌的比较效果 保护肠道免受NEC伤害的配方。目的(3)确定最佳剂量，建立最佳剂量。 保护肠道免受NEC伤害的初步安全性。这个第一阶段的STTR项目将允许MBV和 RINCH收集在第二阶段放大到大型动物模型所需的关键数据，并授权 在第三阶段将技术转让给商业合作伙伴进行商业化。这里建议的产品将是 这是这一未得到满足的临床需求的第一个有效解决方案。

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.