A peptide-based adjuvant therapy to reduce the toxicity of Amphotericin B treatment of invasive fungal infections

The vision of this project is to develop an adjuvant drug to lower the toxicity of the lifesaving but toxic antifungal drug Amphotericin B (AmB). Such a drug would improve outcomes and quality of life for patients affected by invasive fungal infections, including cancer, HIV/AIDS and organ transplant patients and premature babies. The adjuvant drug will be based on our recently discovered, first-in-class peptide synergist of AmB1,2, called Lactofungin (LFG). The proposed project builds on our in-vitro synergy data showing that LFG and a shorter variant LNL increases AmB’s potency 4 to 16-fold in the clinically relevant pathogens Candida albicans, Cryptococcus neformans and drug-resistant Candida auris (Appendix 1, Fig 1). We have also gained first insights
into the mechanism of AmB/LFG(LNL) synergy showing it is selective for lipids in fungal cells over the lipids in mammalian cells (Appendix Fig 2). Funds from this grant will be used to validate our research direction by in-vivo testing LFG and LNL in wax moth larvae and gather a first set of toxicity data in human liver, kidney and red blood cells, and assess serum stability. This proof of principle data is critical to attract the research funds required for translating our innovation into preclinical research and