Malaria is considered today a major threat to the life of millions of human beings in various sections of the world. New chemotherapeutic strategies are in increasing demand and so are basic studies which could provide the requisite scientific background. The present work is an attempt to study, at the molecular level, the role of the host cell membrane in the intraerythrocytic growth and propagation of the human malaria parasite P. falciparum. The ultimate goal is to provide a rational basis for the design of drugs or vaccines which will control parasite development at the various stages of the erythrocytic cycle. The project is based on the knowledge that marked alterations in the permselectivity properties of the host cell membrane appear at the advanced stages of parasite growth. The proposed investigation will concentrate on the following: (a) The role of host cell membrane in controlling the parasite microenvironment in terms of (i) stage relationship of permselectivity changes; (ii) the definition of the chemical, biochemical and biophysical nature of the changes; and (iii) the determination of the physiological role of these changes to parasite growth. (b) Development of chemical and immunological means to specifically arrest intraerythrocytic parasite growth. This encompasses three basic strategies: (i) design of antimalarial drugs which gain preferential access to infected cells (using the information gained from (a)); (ii) design of specific blockers of new permeation pathway appearing in the host membrane of infected cells; and (iii) the use of polyspecific sera from infected hosts and immunized animals and monoclonal antibodies against antigens of parasitic origin appearing on the surface of the host cell membrane. The present constitutes a previously unexplored approach for the chemotherapeutic and immunological control of asexual malarial parasites, involving and interdisciplinary effort by an established laboratory in membrane transport and molecular properties of malaria.
| Loyevsky, M; Cabantchik, Z I (1994) Antimalarial action of hydrophilic drugs: involvement of aqueous access routes to intracellular parasites. Mol Pharmacol 45:446-52 |
