AMINOSTEROL COMPOUNDS AS THERAPEUTICS FOR ASTHMA

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Asthma is a complex inflammatory disease of the airway. Current treatments employ the use of inhaled bronchodilators and corticosteroids. While these medicines are effective for most cases of asthma, they are less effective in severe forms of the disease. Moreover, the chronic use of corticosteroids has been associated with side effects in a subset of patients. Therefore the development of novel medications that are effective in suppressing the asthmatic response and lack the pharmacological properties of corticosteroids is desirable for the treatment of this disorder. We have identified a novel class of low molecular weight molecules that have potent effects on blocking lymphocyte heterotypic aggregations in vitro. in vivo data suggest that these compounds have potent activity in suppressing asthmatic-like responses to antigen in rodent models of asthma. Using combinatorial approaches and structure activity relationships in vitro, we have developed new analogs of the prototype that have more potent activity in suppressing lymphocyte aggregation in vitro. The aims of this grant are: 1) prepare analytically pure preparations of the aminosterol prototype and its analogs for in vivo toxicity studies; and 2) perform in vivo studies with these compounds to determine their efficacy in suppressing asthmatic-like responses to antigen. PROPOSED COMMERCIAL APPLICATIONS: The use of novel low molecular weight compounds that are able to suppress the asthmatic response to antigen via non-corticosteroidal mechanisms have a broad potential for commercialization as new anti- inflammatory and asthma medicines. It is our intent to pursue the generation and development of these aminosterol compounds as an aerosol or oral medication for the treatment of asthma. Magainin is in a unique position to develop compounds of this class because of our intellectual property position, which is secured by multiple patents that cover composition of matter and their use in a broad range of indications.