The long term objective is to define how to use small molecule mimetics of superoxide dismutase (SOD) and catalase to block the oxidant stress component involved in the development of bronchopulmonary dysplasia in premature infants. Reactive oxygen species have been implicated in the formation of bronchopulmonary dysplasia (BPD). They propose testing the efficacy of a class of new, novel compounds in BPD through use of the Bronchopulmonary Resource Center in San Antonio. The lung protects itself against reactive oxygen species under normal conditions with endogenous antioxidant enzymes including superoxide dismutases and peroxidases. Recently, recombinant human Mn SOD introduced into lung airways was shown to diminish alveolar inflammation and protect against the toxicity of hyperoxia in both mice and baboons. They have been exploring manganic porphyrins as mimetics of SOD activity and find them to be markedly effective in diminishing the consequences of oxidative stress in both prokaryotic and eukaryotic cells and in vivo models. Their specific goals in this application are to: 1) determine the developmental biology of the superoxide dismutases and nitric oxide synthase in subhuman primates to assess whether or not deficiencies in specific antioxidant enzymes contribute to the development of bronchopulmonary dysplasia: 2) optimize the dosing and therapeutic pathway for the administration of mimetics of superoxide dismutase; and 3) demonstrate their efficacy in a primate model of bronchopulmonary dysplasia. They expect these studies to provide a novel new therapeutic approach to block the formation of this devastating disease of premature infants.
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