Oral recombinant human lactoferrin (RhLF) in a non-human primate model of asthma

Abstract

Rationale RhLF is an anti-inflammatory and immunomodulatory protein previously demonstrated to block early and late phase asthmatic responses (EAR, LAR) and delayed airway hypersensitivity (DAH) to allergen in a sheep model of asthma. In this study, we evaluated the efficacy and dose range of rhLF in a primate model of asthma. Methods Dust mite-sensitized cynomolgus monkeys were administered liquid rhLF or placebo orally once per day for 14 days. Early phase changes in airway resistance (R aw) and dynamic compliance (C dyn), and cellular composition of bronchoalveolar lavage fluid (BALF) 48-hours after challenge were measured. Results Oral rhLF inhibited up to 75% of the allergen-induced increase in R aw and decrease in C dyn at doses between 9 and 80 mg rhLF/kg body weight, with partial inhibition at 3 mg/kg. Eosinophilic infiltration of BALF was reduced up to 60% at doses as low as 0.3 mg/kg. In pilot experiments, rhLF also abolished LAR and DAH and prevented a drop in oxygen saturation following allergen challenge. Conclusion Oral rhLF inhibits bronchoconstriction and cellular infiltration in a nonhuman primate model of asthma and holds promise as a novel therapeutic agent for asthmatics. RhLF has been shown to be safe and well tolerated in humans and is currently being tested in a Phase II clinical trial in patients with mild to moderate asthma.