The purpose of this research is to extend work to determine the efficacy of orally administered recombinant human lactoferrin (rhLF) in an established primate model of asthma. Asthma is one of the most prevalent chronic inflammatory diseases in the United States affecting -15% of the population. Despite intensive research on asthma over the past decade the prevalence, morbidity and mortality rates continue to increase in the U.S. and the developed world. Over 1% of total healthcare costs in the U.S. are directed towards the therapy and treatment of this disease. In spite of research efforts, few new drugs have been approved for the treatment of asthma. Corticosteroids and Beta-adrenergic Agonists remain the predominant therapies but unfortunately are not effective in all patients. In addition, corticosteroids are associated with a number of potential adverse side effects including growth retardation in children, osteoporosis, glaucoma and cataracts. There remains, therefore a large unmet medical need for new drugs that can more effectively and safely treat this disease. During a previous study in a sheep model of asthma, inhaled lactoferrin, a naturally occurring immuno-stimulatory protein, was shown to inhibit the inflammation which characterizes asthma. New research by Agennix indicates that orally administered lactoferrin is also effective in treating asthma through a novel mechanism involving the stimulation of IL-18. I1_-18 is a potent cytokine that may serve to shift the TH2 immune response responsible for the inflammation associated with asthma. Given the robust safety profile of orally administered lactoferrin there exists a possibility that lactoferrin may represent an exciting, safe and novel new therapy for asthma. This research will seek to a.) Confirm earlier results in sheep and definitively test the efficacy of orally administered lactoferrin in a non-human primate model, b.) Determine in primates the optimal dose and regimen for using lactoferrin as a treatment for allergen-induced asthma symptoms, co) Further elucidate the potential mechanisms of action of rhLF in asthma, d.) Provide evidence supporting future clinical trials in this indication.
