Introduction and Background of the Project

Introduction
Chagas disease is a neglected tropical disease (NTD) that affects 7 million people, mainly in Latin America. It can cause serious heart problems many years after infection and can be fatal if left untreated. Although treatments exist, they are suboptimal, require a long treatment duration, are associated with serious side effects leading to low compliance, and have not been proven effective in chronic stages of the disease. 

One of the biggest challenges in Chagas disease drug development is identifying medicines that can fully clear the parasite in early-stage drug development. Many drug candidates appear promising in standard laboratory tests but later fail because they do not completely clear the parasite. This high rate of attrition increases overall costs, resources, and time required to develop new treatments, ultimately delaying access to better treatments for patients.
This project aims to enhance and streamline drug discovery for Chagas disease by addressing the more critical question of whether the compound can fully clear the parasite load. By developing advanced laboratory tools that more accurately predict a compound’s ability to eliminate parasites completely, this project  seeks to strengthen the foundation of Chagas disease drug discovery and accelerate the development of safer, more effective treatments.

Project Objective
The main objective of this project is to increase the success rate of Chagas disease drug discovery by identifying promising drug candidates more reliably at an earlier stage.
Specifically, the project aims to:
1-  Develop and validate new laboratory tests that can detect whether a drug candidate has the potential to fully eliminate the parasite.
2-  Use these tests to identify new starting points for future drug development.
3-  Understand why certain drug candidate combinations are especially effective, to design safer and more effective treatments.
By achieving these goals, the project will help ensure that only the most promising compounds move forward in the drug development pipeline. This reduces the risk of late-stage failure and supports the development of treatments that are more likely to prove effective for patients.

Project Design
The project is organized into three coordinated research components.
First, a high-throughput laboratory test is used to rapidly measure how quickly compounds kill the parasites that cause Chagas disease inside human cells. This allows thousands of compounds to be screened efficiently and identifies those with strong anti-parasitic activity.
Second, a complementary imaging-based test examines whether parasites return after treatment is stopped. This step is critical for identifying compounds that truly eliminate all parasites.
Third, the project investigates why certain drug combinations work better than single drugs. By understanding the biological mechanisms behind these effects, researchers can design more effective combination therapies.
Together, these steps form a screening ‘pipeline’ that moves from fast testing to deeper biological understanding, ensuring robust and reliable results.

How can your partnership (project) address global health challenges?

Chagas disease disproportionately affects underserved populations and has received limited investment compared to other infectious diseases. One major global health challenge is the slow and suboptimal development of new treatments for this neglected disease.
This project addresses this challenge by providing researchers with better tools to select the best candidates for development  and to make better use of drug development resources.
The tools developed in this project will be shared openly with the global research community, benefitting not only this project but also other Chagas disease research efforts worldwide. In the long term, this work will contribute to global goals to reduce disease burden and support access to effective treatments.

What sort of innovation are you bringing in your project?

The key innovation of this project is in allowing earlier stage identification of drug candidates that have the potential to completely clear all parasites and a better probability of delivering sterile cure.
The project introduces advanced laboratory assays that can detect very small numbers of surviving parasites, something that conventional tests often miss. These assays combine speed, sensitivity, and scalability, making them suitable for early-stage drug discovery.
Another innovative aspect is the integration of drug combination mechanistic assessments at any early stage of drug development. A better understanding of how drugs work together is expected to open new pathways for the rational development of safer and more effective therapies.

Role and Responsibility of Each Partner

· Nagasaki University leads the project and develops high-throughput screening methods and mechanistic studies.
· University of Dundee develops and applies advanced imaging-based assays to evaluate full parasite clearance.
· Drugs for Neglected Diseases initiative (DNDi) coordinates the project and provides reference compounds and strategic guidance.
· Eisai Co., Ltd. contributes a large compound library for screening and supports assay implementation.
Each partner contributes complementary expertise, ensuring scientific rigour and global relevance.

Others (including references if necessary)

This project aligns with international strategies such as the WHO Neglected Tropical Diseases Roadmap, which aims to eliminate Chagas disease as a public health problem. Results from this work will be published in open-access journals and shared with the global research community.