October 4, 2007 — 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.
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
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."
The work is highlighted in the quarterly magazine of the
Biotechnology and Biological Sciences Research Council (BBSRC) this