Potential drug discovery for leishmaniasis
Leishmaniasis focus on the same drug targets as those drugs used to
treat sleeping sickness and Chagas disease, raising the possibility
of a multi-functional drug that will cure all three tropical
diseases.
Research on the sulphur containing parasitic molecule, trypanothione, which is responsible for these diseases has led to the discovery that these parasites use trypanothione to fend off free radicals and other toxic oxidants produced by the immune system of the infected patient.
Enzymes involved in this process are the primary targets of new drugs, one of which is related to a cancer drug target.
Antimonial drugs effectively neutralise the leishmania parasite's antioxidant defence system allowing the patient to clear the infection. This may explain why so many patients co-infected with HIV fail to respond well to treatment with antimonials.
Professor Alan Fairlamb at the University of Dundee explained that: "Many cases of leishmaniasis in India are now proving resistant to the traditional antimony drugs so new modern drugs are needed soon."
"Resistance to antimonials also involve trypanothione," he said.
Fairlamb now plans for his team to investigate how they use their discovery to reverse resistance to antimonials until better, safer drugs are developed.
Currently, the treatment of Leishmaniasis is limited to four drugs. The first line compounds are the two pentavalent antimonials, sodium stibogluconate (Pentostam) and meglumine antimoniate (Glucantime). Failures and relapses occur in all forms of leishmaniasis and constitute approximately 10-25 per cent of cases. If these drugs are not effective, the second line compounds of pentamidine (Lomidine) and amphotericine B (Fungizone) are used.
The discovery is all the more important considering the treatment of parasitic-based diseases over recent years has undergone a distinct lack of investment by the pharmaceutical companies who argue that research and development is too costly and risky to invest in low-return neglected diseases. Indeed, many drugs effective against tropical diseases are no longer available or in danger of being pulled from the market because they are unprofitable.
The World Health Organization (WHO) estimated less than 10 per cent of the $56 billion (€45.6 billion) spent worldwide each year on health research is directed toward diseases that afflict 90 per cent of the world's population.
US production was stopped of praziquantel, a drug used to treat schistosomiasis, a parasitic disease that can cause chronic liver damage and affects about 200 million people worldwide because it was losing money.
The Lancet compiled data from the US Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products, and reviewed current public and private initiatives through an analysis of recently published studies. They found that, of 1393 new chemical entities marketed between 1975 and 1999, only 16 were for tropical diseases and tuberculosis.
There was a 13-fold greater chance of a drug being brought to market for central-nervous-system disorders or cancer than for a neglected disease.
