Miltefosine – a dual purpose antifungal to mitigate antifungal resistance – Newcastle University

Lead applicant

Professor Janet Quinn – Newcastle University

Co-applicants

Gustavo H. Goldman – University de Sao Paulo

Neil Gow – University of Exeter

Paul Denny – Durham University

Mike Barrett – Glasgow University

Geographical focus –  UK & Brazil

Research Theme – Microbial Pathogenesis

Lay summary

Although often in the shadow of bacterial and viral pathogens, fungi cause a wide range of diseases from the superficial to the lethal, and recent data indicate that invasive fungal infections cause 2.5 million deaths per year. Furthermore, the Antimicrobial Resistance (AMR) time bomb threatens to make this dire situation even worse, with the limited armamentarium available for fungal disease now placed under severe pressure. The prohibitive costs in discovering and developing new drugs, coupled with high attrition rates due to unfavourable pharmacology in humans, demand new ways of approaching this problem and finding rapidly implementable solutions to combat AMR, especially in resource limited settings.Miltefosine is an orally available antimicrobial agent that has been used in the treatment of systemic visceral leishmaniasis (an insect-vector borne protozoal infection) for over 20 years. Miltefosine has curative potential for a number of fungal diseases and has already been approved for use in systemic candidiasis infections. However, a lack of knowledge as to the mode-of-action and spectrum of activity in monotherapy and combination therapy of this WHO Essential Medicine hinders understanding and development. In this project we bring together a cross-disciplinary team of experts in the cell and molecular biology of eukaryotic pathogens to dissect the mechanism of miltefosine against a range of pathogenic fungi, to improve its utility and durability leading to bring near term clinical benefits in LMIC with high burdens of endemic fungal infection.