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Gene 'maps' show way to beat killer diseases

Science Editor,Steve Connor
Friday 15 July 2005 00:00 BST
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Three of the most devastating diseases of the developing world could soon be eradicated after a breakthrough in understanding how they are programmed to be human parasites.

Scientists have decoded the genetic blueprints of the parasitic microbes responsible for African sleeping sickness, Chagas disease and Leishmaniasis, which collectively affect up to 30 million people and endanger the lives of a further 500 million.

Knowing the precise sequence of genetic "letters" that make up the alphabet of the microbes' genes should now allow scientists to design effective drugs and vaccines against the three killers. At present, there are no vaccines or cheap, effective remedies against any of the parasites, each transmitted by the bites of different insects in some of the poorest countries.

More than 250 scientists from 21 nations - including the Wellcome Trust Sanger Institute in Cambridge - helped in the £18m project to decode the genomes of the three single-celled organisms belonging to a family of parasites called trypanosomatids.

Professor Najib El-Sayed, leader of a research team from the Institute for Genomic Research in Rockville, Maryland, said: "Thanks to these studies, scientists are now much closer than they were five years ago to developing effective drugs against these terrible diseases."

African sleeping sickness is caused by the parasite Trypanosoma brucei, which is transmitted by the tsetse fly. It affects many countries in sub-Saharan Africa and causes fevers, headaches, joint pains and itching, followed by debilitating infection of the brain and central nervous system.

Chagas disease is caused by Trypanosoma cruzi, which is transmitted in the bite of a blood-sucking bug that thrives in the cracks and crevices of poor housing in South America. Over many decades, patients suffer severe damage to their internal organs, including the heart and intestines. The final microbe to be decoded is Leishmaniasis, which is transmitted in the bite of tiny sand flies. It causes severe skin disfiguration as well as long-term disease, fever and weight loss.

The research, in the journal Science, shows that each parasite has a set of some 6,200 "core genes" arranged in a similar way that appear to play a vital role in the function of the parasitic organisms. Peter Myler, from the Seattle Biomedical Research Institute said the mapping aids design of specific drugs that target one or all of the three parasites. "Initially, we believed the gene organisation among the parasites would be different, but 70 per cent of the genes occur in the same order," Dr Myler added.

"The core genome of all three is very similar, with the differences mainly at the end of the chromosomes. So this tells us if we focus on the genes that are the same in all three, but different from humans, we have the potential to develop a class of drugs that can target all three diseases." Decoding the genes of the three parasites will allow scientists to understand how they infect people, how they cause human disease and why they are carried and transmitted by different insects.

George Cross, of the Rockefeller University in New York, said that existing drugs may even be useful against the diseases after the biology of the parasites was better understood through the analysis of their genomes.

"Because of their distinct evolution, trypanosomes present a plethora of potential drug targets and potential drugs are almost certainly languishing in the chemical libraries of pharmaceutical companies," Dr Cross said.

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