POTENTIATION OF ANTIMALARIAL OXIDANT DRUGS

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DESCRIPTION (Adapted from the Applicant's Abstract): On a global scale the protozoan parasite Plasmodium falciparum is estimated to cause in excess of 800 million cases of malaria per year. Of this number approximately 150 million individuals develop serious disease with the annual number of deaths caused by P. falciparum is estimated to be 2 million. It is generally believed that the worldwide burden of malaria will increase in the upcoming years because of the continual emergence of drug-resistance strains of P. falciparum and the significant increase in international travel. As a result there is a urgent need for new drugs and more efficient use of existing drugs in areas in which drug resistance has yet to become prevalent. Investigators at INTERLAB have recently discovered a significant synergy between antimalarial compounds of the oxidant class in combination with certain proprietary reagents. The synergy leads to potentiation of antimalarial activity at least 300 fold. The presence of these compounds does not apparently influence the growth and differentiation of normal mammalian cells in vitro and thus may represent an observation of far reaching impact for treatment of malaria. Because of the proposed site of action leading to this antimalarial synergy, it is also likely that this observation will have application in the control of other disease caused by protozoan parasites. Thus, infections caused by Pneumocystis and Cryptosporidium, of special clinical relevance in immunocompromised patients with the AIDS, may be controlled more readily by application of this drug synergy. In this Phase I application they will establish the basis for this observation of antimalarial drug synergy including the response of multiple-drug resistant strains of P. falciparum and will initiate studies designed to determine mechanisms responsible for the synergistic response.