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Innovative lead discovery strategies for tropical diseases

Nature Reviews Drug Discovery volume 5, pages 941–955 (2006)Cite this article

Key Points

  • There is a continuing and compelling need for new and improved treatments for tropical diseases, including tuberculosis, malaria, African sleeping sickness, leishmaniasis, Chagas disease, onchocerciasis, lymphatic filariasis and schistosomiasis.

  • Existing drugs have issues that limit their utility in resource-poor settings, such as high cost, poor compliance, drug resistance, poor efficacy and low safety.

  • Discovering lead compounds with the potential to become usable drugs is a crucial step to ensuring a sustainable global pipeline for innovative products for tropical diseases.

  • To achieve this, there is an urgent requirement for a coordinated approach involving multi-disciplinary networks of investigators, as well as partnerships between industry and the public sector in both developed and developing countries.

  • This paper discusses strategies to meet the need for lead compounds for tropical diseases. Specific examples are drawn from the work of the WHO/TDR covering a broad range of tropical diseases and from the approaches taken by other agencies in these areas.

  • The discovery of novel therapeutics for tropical diseases has largely relied on three strategies: extending the indications of existing treatments for other human and animal ailments to tropical diseases; 'piggy-back' discovery (when a molecular target present in parasites is being pursued for other commercial indications, thereby facilitating the identification of chemical starting points) and de novo drug discovery. This paper describes how these strategies can be integrated in network and partnership models.

Abstract

Lead discovery is currently a key bottleneck in the pipeline for much-needed novel drugs for tropical diseases such as malaria, tuberculosis, African sleeping sickness, leishmaniasis and Chagas disease. Here, we discuss the different approaches to lead discovery for tropical diseases and emphasize a coordination strategy that involves highly integrated partnerships and networks between scientists in academic institutions and industry in both wealthy industrialized countries and disease-endemic countries. This strategy offers the promise of reducing the inherently high attrition rate of the early stages of discovery research, thereby increasing the chances of success and enhancing cost-effectiveness.

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Figure 1: An innovative lead discovery strategy for tropical diseases.
Figure 2: WHO/TDR-funded compound evaluation network.
Figure 3: The growing WHO/TDR drug discovery portfolio.

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Acknowledgements

The authors would like to thank R. Ridley, A. Oduola and J. Lazdins for their support, A. Fairlamb and T. Wells for critically reading the manuscript. We also thank F. Fakorede, M.-A. Mouries, C. Alias and L. Swarb for their help with the paper.

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Authors and Affiliations

  1. Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland

    Solomon Nwaka & Alan Hudson

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  1. Solomon Nwaka
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Correspondence to Solomon Nwaka.

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FURTHER INFORMATION

Medicines for Malaria Venture

Grand Challenges in Global Health — Limit Drug Resistance

EU Commission — Poverty-Related Diseases

EU Commission — New TB Drugs

Bill & Melinda Gates Foundation: Call For Proposals – Tuberculosis

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Nwaka, S., Hudson, A. Innovative lead discovery strategies for tropical diseases. Nat Rev Drug Discov 5, 941–955 (2006). https://doi.org/10.1038/nrd2144

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