Towards the development of a clinically and regulatory approvable treatment for Necrotizing Enterocolitis (NEC)

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NEC is a severe neonatal condition that commonly affects premature neonates with significant morbidity and mortality (up to 50% in patients requiring surgery, with limited improvement in the last 30 years). The pathogenesis is not completely understood, but it is known to be associated with poor intestinal perfusion, bacterial translocation and progressive inflammation ultimately leading to necrosis and/or intestinal perforation1,2. Presently there are no effective treatments for NEC. The economic cost of NEC accounts for ~ 19% of neonatal expenditures and an estimated $5-6 billion per year for hospitalizations in the United States. Thus, NEC has major implications for the patient, their family and society as a whole3.The UCL team together with Micregen (non-academic partner) have shown that the secretome produced by amniotic fluid stem cells (AFSC) alter key cell activities in mouse model of NEC leading to greatly improved tissue structure and function2,4,5. As a step towards translation towards clinical use, Micregen have developed a novel AFSC therapeutic (development name MRG1061) which can be produced at scale to GLP/GMP standards. This has demonstrated an ability to attenuate disease severity in the mouse NEC model. Micregen have held two scientific advice meetings with the Medicines and Healthcare products Regulatory Agency (MHRA) with the aim of developing a Phase I/II clinical trial in partnership with UCL. One of the key recommendations from the MHRA was the need for a portfolio of evidence for efficacy and dosing a secondary rodent model of NEC (namely the rat model).This project will generate key data, essential for developing a clinical trial for NEC by determining the effectiveness and optimal dosing, route of administration as well as formulation of MRG1061 in treating rat model of NEC.