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Where: At the McGill University Health Centre (MUHC), Glen Site, block D, room S1.1427, 1001 Decarie Boulevard, Montreal, Quebec H4A 3J1
When: Wednesday, October 2, 12 p.m.
Speaker: Patrícia Sampaio Tavares Veras, MD, PhD
Gonçalo Moniz Institute - Oswaldo Cruz Foundation
National Institute of Science and Technology of Tropical Diseases
LeishDerm:an HSP90 inhibitor-based formulation cures experimental cutaneous leishmaniasis by parasite killing and modulating host immune response
The chemotherapy currently used to treat leishmaniasis presents several limitations, which leads to recurrence. Therefore, the development of new interventions to treat this disease is crucial. Our identification of molecular targets in Leishmania infection for chemotherapeutic intervention focused on the activity of the molecular chaperone heat shock protein 90 (HSP90), which is involved in proteins folding. Our group previously demonstrated the efficacy of an HSP90 inhibitor against Leishmania spp. and recently tested the efficacy of an aqueous-soluble HSP90 inhibitor, INH2, in an experimental cutaneous model. At early stages of infection, a significant reduction in lesion size and the complete clearance of parasite load in the ears and draining lymph nodes of most animals was observed, in addition to reduce in vitro cytokine production (IL-10, IL-6, IFN-γ and TNF) by lymph node cells. Moreover, macrophages from NLRP3-KO C57BL/6 mice treated in vitro with INH2 exhibited a delayed ability to control infection compared to WT cells. These data indicate that INH2 is a potent antileishmanial, which also modulates inflammatory host responses that could contribute to infection resolution.
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