Genetic codes of three deadly parasites cracked
Scientists have decoded the entire genetic sequences of parasites that cause three of the deadliest diseases in the developing world — leishmaniasis, sleeping sickness and Chagas disease.
The sequences were published today (14 July) by Science.
Completing the sequences is a "major milestone in the field of genomics" that could lead to better methods of diagnosis and new treatments and vaccines, said one of the lead researchers, Najib El-Sayed of US-based The Institute for Genomic Research (TIGR), at a press conference in London yesterday.
By comparing the three genetic sequences, the researchers found that they have about 6,200 genes in common. Research to identify drug targets will focus on these shared genes.
Finding one drug that could work against all three is important, given the limited resources to fight these diseases, El-Sayed told SciDev.Net.
The three 'neglected' diseases kill more than 150,000 people every year, yet research into them has been limited.
There are no vaccines, doctors use outdated methods of diagnosis, and the drugs used to treat infected people are often toxic. The arsenic-based drug melarsoprol kills one patient in every twenty given it to treat sleeping sickness, caused by the parasite Trypanosoma brucei.
Sanjeev Krishna, who researches the disease in Angola, told the press conference that its "nightmarish qualities" include coma and often death, and even those who recover are at high risk of brain damage.
Chagas disease, triggered by the Trypanosoma cruzi parasite, is widespread in Latin America, and can lie undetected in patients for decades before re-emerging to cause severe internal damage.
The third parasite, Leishmania major, causes severe skin disease that can leave infected people heavily scarred.
|Lutzomyia longipalpis, |
a sandfly vector of Leishmania
parasites, taking a blood meal
through human skin
Comparing all the parasites' genetic sequences threw up some surprises, El-Sayed told SciDev.Net.
For example, the parasite that causes sleeping sickness evades our immune systems by creating a 'smokescreen' of millions of molecules on its surface.
The scientists found that many of these are made by combining the products of 'pseudogenes' — genes that are no longer fully functional, but which can still make fragments of proteins.
There are so many combinations of these fragments available that the parasite can keep changing the types of molecules appearing on its surface. This allows the parasite to continually evade being detected and destroyed by the immune system.
Matt Berriman of the Wellcome Trust Sanger Institute, based in Cambridge, United Kingdom, said that these surface molecules are arranged in such a complex way that scientists are unlikely to find a single parasite antibody that could form the basis of a vaccine.
Berriman says the next step for drug researchers is to discover the function of genes all three parasites share by blocking them and seeing what effect this has on the parasites.
The sequences also hold promise for the development of modern methods of diagnosis.
One method of diagnosing sleeping sickness used today dates back to the 18th century, which Krishna says means that the accepted figure of 50,000 people with sleeping sickness worldwide is likely to be a huge underestimate.
Despite the research breakthrough that these sequences provide, the lack of financial incentives for pharmaceutical companies means that developing new treatments will not be easy.
Public-private partnerships are therefore likely to be the only way the research can progress, El-Sayed told SciDev.Net.
Yesterday, for instance, one such partnership was announced between the Drugs for Neglected Diseases Initiative and the Kitasato Institute in Japan. The two organizations are to join forces to find a treatment for sleeping sickness.
The Kitasato Institute will test 300 to 400 natural substances, including traditional Japanese and Chinese herbal medicines and plant extracts, for efficacy against Trypanosoma brucei.
The US$32 million sequencing project involved a major collaborative effort of scientists from the Sanger Institute, the US-based Seattle Biomedical Research Institute and The Institute for Genome Research, and the Karolinska Institute in Stockholm.
Peter Myler of the Seattle institute said that, importantly, researchers from developing countries where these diseases are prevalent were heavily involved in the collaboration. Brazil for example, made a significant contribution to mapping the sequences.The sequence data is available through the websites of TIGR and the Wellcome Trust Sanger Institute.
Link to full paper comparing the three parasite's sequences by El-Sayed and colleagues in Science.