Research Project
6833584
DESCRIPTION (provided by applicant): This feasibility study is based on our hypothesis that recombinant human lactoferrin [rhLF] can prevent or reduce severity of necrotizing enterocolitis [NEC]. NEC is mainly a disease of very low birth weight [VLBW] human infants. It is a leading cause of morbidity and mortality in neonatal intensive care units, with incidence of approximately 10 percent in VLBW infants and mortality of about 25 percent. Hospital costs associated with surgical and medical NEC are very high. Studies show NEC occurs less frequently in breast fed infants. Sufficient amounts of a mother's milk are often not available to prevent abnormal bacterial colonization and to enhance gut development in the crucial days following birth. We anticipate that all VLBW infants would benefit from receiving rhLF for at least 4 weeks after birth or until full human milk feedings are established. Biotechnology has made rhLF available for drug development. LF is known to have anti-bacterial, anti-inflammatory and immuno-stimulating properties. It also promotes gut epithelial growth. Using a neonatal rat model of bacterial translocation, we have shown already that rhLF is highly effective in decreasing bacteremia, illness and death from Escherichia coil-related intestinal infection. Formula-fed newborn rats exposed to hypoxia develop an intestinal disease similar to human NEC. As rat milk does not contain LF, we plan to use this long-accepted neonatal rat model to test whether adding rhLF could prevent or attenuate this disease. Our primary specific aim is therefore to show the efficacy of oral rhLF in preventing or attenuating NEC in the newborn rat model. Secondary aims, utilizing the tissues obtained from animals used in the primary specific aim, will continue beyond the time-frame of this application to explore the mechanisms by which the benefits of rhLF might occur. The data generated by this research are essential for the FDA to grant Investigational New Drug [IND] status for rhLF, and thus enable a NEC clinical trial in human neonates.
