Principal Investigator (PI)
Harvard T.H. Chan School of Public
The Foundation is providing £229,579 in support.
Margarida Ruivo - Inés Marreiros
GSK´s in-kind contribution to the project will include access to the GSK-Tres Cantos animal facilities providing the malaria animal models to be employed in the project, as well as the technical expertise, equipment, and reagents (bioimaging, flow cytometry, qPCR) to assess the parasite´s ability to infect and develop in liver cells.
The insectary unit available in Tres Cantos will also be critical for providing all the sporozoites needed for the project.
GSK-Tres Cantos has a wide experience in parasitology and development of animal models for drug discovery purposes in which they have focused mainly in the translation of PK-PD predictions from animals to humans.
Despite a remarkable recent reduction in the global burden of malaria, there remains an urgent need for novel anti-malarial drug treatments. Chemoprophylaxis remains the mainstay for malaria prevention, but its efficacy is compromised by non-adherence to medication. A safe and effective long-acting intramuscular (LAI) drug-dosing preparation would provide a promising approach to deliver a new medicine vision for malaria control and eradication.
A significant gap not yet addressed by drug discovery scientists is the understanding of the evolution and impact of drug resistance in liver stages of Plasmodium. Liver-stage parasites are an important reservoir of infection, but because there are far fewer of them compared to blood stage parasites it makes the development of drug resistance at this stage less likely but still possible.
This project will provide insights regarding the development of drug resistance in liver stages and will evaluate the impact of pre-existing resistance for dose prediction of new drug classes targeting bc1 in the context of chemoprophylaxis.
The long-term goal of this project is to understand basic molecular mechanisms of drug resistance in the different stages of protozoan parasites with the aim of applying the best preventive and therapeutic interventions against infection.