Preclinical Development of Novel Liver-Stage Active Antimalarials with Radical Cure Potential
Abstract
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. Our novel acridone chemotype represents a broad-spectrum approach with the potential to vanquish those challenges. In the previous project period, our approach was aggressive and rigorous, with extensive multi-stage evaluations and lead optimization processes. We have selected a preclinical candidate with promising attributes. The specific goal of this FY21 Expansion Award project is to conduct extensive and comprehensive preclinical evaluations of our late lead acridone candidate, and ultimately, we envision identifying and producing an antimalarial acridone candidate that warrants clinical development in phase 1 and phase 2 trials. 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.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210494
Entities
People
- Jane X Kelly
Organizations
- Portland VA Research Foundation
- United States Army