Leishmaniasis drug discovery: recent progress and challenges in assay development

Area of Science:

• Parasitology
• Tropical medicine
• Drug discovery

Background:

• Leishmaniasis is a growing global health threat, endemic in 98 countries.
• Existing treatments for leishmaniasis face challenges from drug resistance and toxicity.
• There is an urgent need for novel anti-leishmanial compounds with new mechanisms of action.

Purpose of the Study:

• To review the current landscape of leishmaniasis drug discovery.
• To compare existing and emerging assay technologies for identifying anti-leishmanial agents.
• To highlight the need for more physiologically relevant assays.

Main Methods:

• Literature review of leishmaniasis disease burden and current treatments.
• Comparative analysis of various in vitro and in vivo assay formats.
• Evaluation of assay technologies for drug discovery pipeline suitability.

Main Results:

• Current in vitro assays show limited success in translating to clinical efficacy.
• High attrition rates are observed for compounds identified through traditional screening methods.
• Physiologically relevant assays are crucial for improving the success of anti-leishmanial drug discovery.

Conclusions:

• Developing novel anti-leishmanial drugs is critical due to resistance and toxicity issues.
• Current drug discovery assays require significant improvement in predictive power.
• The review emphasizes the importance of advanced, relevant assay technologies for future leishmaniasis treatment development.