Breakthrough for Scientists in Fight Against Malaria Parasite

Researchers have opened the way for new treatments of malaria, the scourge that threatens 500 million worldwide and kills a child in Africa every 30 seconds.

Scientists in Thailand and Edinburgh have worked out why some drugs work against the malaria parasite, and some do not. In October geneticists completed the entire DNA sequence of both the malaria parasite, and one species of mosquito that carries the infection.

The research confirmed what doctors in the field already knew: that malaria is a fiendishly cunning enemy. The parasite Plasmodium falciparum seems to be able to hide from vaccines, and to outwit each new generation of drugs.

But somewhere in the mass of data within two genetic sequences, researchers felt, was the key to a new set of weapons. One scientist said at the time: "We have presented them with a haystack, and now they have to go and find the needle."

The search for the needle goes on. But the institute for cell and molecular biology at the University of Edinburgh, and the national centre for genetic engineering and biotechnology in Bangkok, may have found out precisely where to stick it when they find it. They now know what happens to make strains of malaria become resistant to one group of the most effective drugs.

Yongyuth Yuthavong in Bangkok and Malcolm Walkinshaw in Edinburgh report in the journal Structural Biology that the parasite routinely produces a protein, known only as DHFR, to keep itself alive. The drug pyrimethamine blocks the function of DHFR and thus controls the infection. But use of pyrimethamine has been widespread over the last 40 years, and inevitably, the parasite has developed resistance. It did so, according to the two researchers, by altering its DHFR. They genetically engineered laboratory bacteria to produce large quantities of DHFR, and then studied the way the protein can change to protect itself. They discovered that it was always the same part of the protein that changed. Once scientists begin to understand what changes, and why, they can start to think about designing new weapons to outwit the parasite.

"We can now use this protein structure to design a new generation of drugs which makes it possible to overcome resistant strains of malaria. People have studied this protein for a long time, but until now, no one has been able to determine its detailed structure," Prof Walkinshaw said.