Potential new drugs for tropical disease leishmaniasis

The fight against the deadly tropical disease Leishmaniasis, also known as black fever, has been boosted by scientists at the University of Durham, whose new screening system has raised the possibility of new, safer drugs.

The work is highlighted in the quarterly magazine of the Biotechnology and Biological Sciences Research Council (BBSRC) this week.

Leishmaniasis is a parasitic disease found largely in the tropics which the World Health Organisation has estimated infects 12 million people worldwide each year. In the tropical regions Leishmaniasis is transmitted by sandflies but more recently cases have been reported in Europe among intravenous drug users with HIV. The parasite is a protozoan, a single-celled microbe, which causes symptoms ranging from skin sores to a swollen spleen or liver. If not treated, the more damaging forms of the disease can lead to death.

Many drugs against these types of parasites have toxic side effects, and can result in the death of one in ten patients. Development of safe treatments has been hampered up by the similarity between the biochemical processes of the pathogen and its human host.

However, researchers at Durham University have now developed a screening system to provide new insight into the biochemical processes at play. As a result they have identified and characterised a key enzyme which helps produce an essential cell component of protozoa called a ‘complex sphingolipid', plus an inhibitor which specifically acts against this enzyme. The team have recently filed a patent for the system, which could be used in the search for non-toxic anti-protozoan drugs.

Dr Paul Denny, research leader, explains: “Identifying both the enzyme responsible for the complex sphingolipid component of protozoa plus the inhibitor which acts against this enzyme is very significant. It has marked implications in the search for anti-protozoan drugs with reduced side-effects, as knowing how to block this enzyme could prevent the production of the complex sphingolipid and thus prevent the protozoa from establishing infection.

“Potentially we can rapidly screen thousands of compounds for inhibitory effects against this enzyme. It provides a much quicker means of identifying inhibitors with the potential for drug development than is standardly used.

“Our next step is to understand the structure and mechanism of this enzyme to help inform rational drug design.”

The research is supported by BBSRC. Prof Nigel Brown, BBSRC Director of Science and Technology commented: “Leishmaniasis is an extremely damaging disease which threatens 350 million people in 88 countries around the world. This research demonstrates how important fundamental bioscience research is to developing life-saving pharmaceuticals, and should provide hope to people in affected regions.”