New Strategies for Drug Discovery and Development for Plasmodium Falciparum
Abstract
Malaria continues as a major health threat throughout the tropical world and potential demand for antimalarials is higher than for any other medication yet the world faces a crisis--drug resistance is emerging and spreading faster than drugs are being developed and the flow in the pipeline of new drugs has all but stopped. This represents a particular threat to the U.S. Military. A new strategy for drug development is urgently needed. Current drugs are based on a small number of target molecules or lead compounds and in most cases the target of drug action is yet to be identified. Resistance is emerging rapidly and the mechanisms of resistance are poorly understood. The identification of new targets or new candidate drugs, based on an understanding of the parasite biology, are key elements in this new strategy. The goal of this work is to use a molecular genetic approach both in the identification of new drug targets and in the investigation of mechanisms of drug resistance. There are two parallel approaches being developed, one the development and characterization of a homologous transformation system, and two the development of a heterologous expressions system in yeast for potential drug target enzymes. The yeast expression system should allow rapid screening of new drugs, greatly increasing the rate at which new antimalarials can be tested and developed. Both of these approaches are based on the functional analysis of malaria genes with goal of using this information in the identification and development of new antimalarial drugs. The recent initiation of the Plasmodium falciparum genome project will complement this project in that new potential targets will be identified and the methodologies developed because of the crisis facing us in antimalarial drugs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1998
- Accession Number
- ADA366070
Entities
People
- Dyann F. Wirth
Organizations
- Harvard University