Preclinical development of novel liver-stage active antimalarials with radical cure potential

This application, titled “Preclinical Development of Novel Liver Stage Active Antimalarials with Radical Cure Potential,” supports studies that will make an important contribution toward research for disease control related to the following FY21 PRMRP topic area: Malaria. It specifically addresses the Area of Encouragement: Identification of novel and/or innovative malaria drug targets for blood- and liver-stage malaria parasites. Malaria remains one of the deadliest diseases in the world today, as it has been so for thousands of years. The demoralizing impact of the disease extends beyond the annual body count to effects on family and social structure, on sustained poverty in endemic areas, and on creating untold suffering for nearly half of the world’s population. The situation is worsening due to the emergence and spread of strains of malaria parasites that harbor resistance to multiple drugs, including the front-line antimalarial combination therapy. If the global effort to eradicate malaria is to be successful and sustainable, both prevention and treatment must address the gaps and weaknesses in the armamentarium of available therapies. Ongoing needs include affordability, safety for the most vulnerable patients, single-dose treatment, aptitude for killing liver-stage parasites with relapse prevention, low susceptibility to drug resistance, and the ability to block transmission. The novel acridone chemotype represents a broad-spectrum approach with the potential to vanquish those challenges. In the previous project period, the approach was aggressive and rigorous, with extensive multi-stage evaluations and lead optimization processes to select a preclinical candidate with promising attributes. This research project builds upon a continuous collaboration between Portland VA Research Foundation and Walter Reed Army Institute of Research. The choice of a Partnering PI approach reflects the different sets of expertise that will be needed for successful completion of the project plan. The nature of the project will require the two laboratories to work together simultaneously and synergistically for extensive preclinical evaluations. Thriving on rapid information feedback and open communication between collaborators, our collaborative team has a long and fruitful history with great proven success.

Drug-based Strategies
Product Development

Oct 2021 — Sep 2022

$350,010

United States