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.”
Source : Biotechnology and Biological Sciences Research Council. October 2007.
