Development of Novel Approaches to Combinatorial Antifungal Drug Therapy

This invention relates to a method of treating fungal infections. Fungal infections can be life-threatening to transplant patients, cancer chemotherapy patients, AIDS patients and others in immunocompromised conditions. Pathogenic fungi represent an increasing clinical challenge because existing antifungal agents are hampered by issues of efficacy, toxicity and the development and/or discovery of strains that are resistant to current antifungal drugs. This novel treatment involves administering a combination of compounds that inhibit the activity or expression of the fungal proteins FKBP12 and homoserine dehydrogenase. Evidence indicates that inhibition of the proteins FKBP12 and homoserine dehydrogenase is lethal to fungi by causing an accumulation of toxic levels of the homoserine dehydrogenase substrate, aspartate beta-semialdehyde, or a derivative thereof. As this combination therapy targets a biosynthetic pathway, that is conserved in fungi but not in mammals, it should be active against a broad range of fungal species and toxicity to the patient should be minimal. Description (Set) Proposed Use (Set) This invention may provide a novel broad-spectrum antifungal therapy with minimal toxicity in patients.

Inventor(s): Boeke, Jef D.

Type of Offer: Licensing



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