Preclinical assessment of aspartyl protease inhibitors as an antifungal therapeutic strategy

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Challenge: A need exists for new drugs efficiently targeting fungi such as Candida albicans, which affects thousands of patients on its own every year in Canada and over the world. Similarly, to antibiotics, fungi also show an increase in resistance against first-line therapeutic agents, including some that are considered as major treats to public health.

Solution: The research team selected a virulence factor that contributes to the fungal dissemination as a new molecular target and developed inhibitory compounds with a great in vitro efficacy. Preliminary data suggest that these new antifungal molecules will be more efficient when used in combination with other drugs acting on different targets. This approach has the potential to improve efficacy and to reduce toxicity when compared to current therapies. This project aims to identify a new antifungal drug and an appropriate combined therapy that could be tested in a Phase I clinical trial. To succeed, the team will first validate the approach by using in vitro experiments, and then identify the clinical use for which the new drug would be the most efficient for. To this regard, the research team will test the therapies in six different animal models exploring several infection scenarios, and evaluate topical vs systemic therapy as well as acute vs long-term therapy.

Expected Achievements /Impacts: The project results will contribute substantially to the research field of fungal biology and therapy, since this project could also lead to an increased efficacy against resistant fungi. The tools and knowledge developed could also contribute to the onset of new molecular entities against other fungal targets. Overall, this project will allow to add and validate new molecules within the JCT Biotechnologies company’s pipeline, and to identify and improve lead components to better target fungi like Candida or Malassezia that are problematic in patients suffering from various diseases. This study will help attract investments to continue the development of new therapies while providing patients with early access to new therapies.

Principal Investigator:
Éric Rhéaume
Montreal Heart Institute
Co-Investigators:
Adnane Sellam / Montreal Heart Institute
Project of
$1,212,264 over 3 years
Supported by CQDM through :
– Ministère de l’Économie, de l’Innovation et de l’Énergie du Québec (MEIE)
And by co-funding partner:
– JCT Biotechnologies
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