Grant: Proof of Principle Program - Phase I

Lung infections are one of the most important causes of death in patients whose immune systems do not work properly because of chemotherapy, organ and bone marrow transplantation or the use of immune suppressing medications like steroids. These infections are also common in people with long standing lung disease from smoking or other toxic exposures. One of the most important causes of lung infection in these patients is the mold Aspergillus. Despite antifungal treatment up to half of people will die when infected with this organism. Even when antifungal treatment for these infections is successful in the short term, it does not eliminate the organism from the lung and as a result these infections commonly recur. This resistance results from the ability of these bugs to build a slime coating that is highly resistant to antifungals as well as our own immune system. To combat these deadly infections, our group has developed slime-degrading enzymes, which selectively target, penetrate, and destroy this slime coating without causing damage to our own cells. In a test tube this treatment results in the elimination of the slime, allowing Aspergillus to be targeted and killed by our defensive immune system and antimicrobials. In this proposal we will optimize and test these enzymes, in mice infected with Aspergillus. This novel treatment will have tremendous potential to improve the lives of patients poorly functioning immune systems or with long standing lung disease.