Researchers find new way to attack malaria parasite, cure disease in monkeys

Thursday, February 14th 2002, 12:00 am

By: News On 6

WASHINGTON (AP) _ Researchers have found a new class of drugs that in laboratory animals can cure malaria, a mosquito-borne disease that kills more than 2 million people annually.

The drug, called G25 by the French team that developed it, disables the spread of the malaria parasite by blocking its ability to make copies of itself inside the red blood cells of victims.

In laboratory studies, the researchers report Friday in the journal Science, small doses of G25 were able to cure infections of two types of malaria in two types of monkeys. The experiments also suggested that the drug has a very low toxic effect, the researchers said.

``This is a very important step because they showed it worked in two types of monkeys,'' said Carole Long, a malaria researcher at the National Institute of Allergy and Infectious Diseases, one of the National Institutes of Health.

The researchers, led by Henri J. Vial of the University of Montpellier in France, report that G25 attacks malaria by interrupting a key part of the parasite's life cycle.

Malaria spreads by a protozoan parasite that has three stages in its life cycle.

It is introduced into a victim by a mosquito bite. As the mosquito takes in blood, it pumps in a blood-thinning saliva that contains the parasite.

Once inside the body, the parasite rides the bloodstream into the liver, where it burrows and multiplies into a cluster of thousands of parasites. The clusters burst after a few days and the new parasites invade red blood cells and start another stage of the life cycle.

Inside the blood cell, the parasite multiplies again, making hundreds of young parasites. When the blood cell bursts, other blood cells are infected. Eventually, up to 70 percent of the victim's red blood cells can be destroyed, leading to severe anemia, fever and death.

If a victim is bitten by a mosquito, the insect can pick up the parasite along with the blood and the malaria life cycle starts over.

The G25 compound works by blocking the parasite's attempts to multiply inside the blood cells.

To reproduce, the parasite must synthesize fats that become part of the protective membrane for each of its progeny. G25 prevents the parasite from making this membrane, thus blocking reproduction.

Vial said in Science that although G25 blocked the fat, or lipid, synthesis of the parasite, it had no effect on the host red blood cell.

``If you prevent the parasite itself from synthesizing lipids, it will not survive,'' Vial said.

NIH researcher Long said the work is significant because it attacks the malaria parasite in a new way. The malaria parasite is becoming increasingly resistant to many of the drugs now used to control or treat the disease and ``we need new classes of drugs.''

Long said Vial and his colleagues ``have made significant advances in moving this toward actual drug development. I am cautiously optimistic.''

She noted, however, that more research must be done, particularly studies on toxicity, before the drug could be ready for human studies.

One drawback of the drug, experts said, is that it must be injected. Vial said in Science that his team hopes within two years to develop a version of G25 that can be taken orally.

There are an estimated 300 million to 500 million new malaria infections worldwide each year, mostly in Africa and Southeast Asia. The majority of the 2 million who die annually from malaria are children.