Why hasn’t there been more progress in new Chagas disease drug discovery?

ABSTRACT

Introduction: Chagas disease (CD) is a neglected disease caused by the protozoan parasite Trypanosoma cruzi. In terms of novel drug discovery, there has been no progress since the 1960s with the same two drugs, benznidazole and nifurtimox, still in use. The complex life cycle, genetic diversity of T. cruzi strains, different sensitivities to the available drugs, as well as little interest from pharmaceutical companies and inadequate methodologies for translating in vitro and in vivo findings to the discovery of new drugs have all contributed to the lack of progress.

Areas covered: In this perspective, the authors give discussion to the relevant points connected to the lack of developments in CD drug discovery and provide their expert perspectives.

Expert opinion: There are few drugs currently in the preclinical pipeline for the treatment of CD. Only three classes of compounds have been shown to achieve high cure rates in mouse models of infection: nitroimidazoles (fexinidazole), oxaborole DNDi-6148 and proteasome inhibitors (GNF6702). New biomarkers for Chagas’ disease are urgently needed for the diagnosis and detection of cure/treatment efficacy. Efforts from academia and pharmaceutical companies are in progress and more intense interaction to accelerate the process of new drugs development is necessary.

KEYWORDS:

• Chagas disease
• drugs
• neglected disease
• Trypanosoma cruzi

Article Highlights

• Benznidazole and nifurtimox, both used since the 1960s, are the only drugs available for the treatment of this disease.

• Only a few drugs are in early preclinical evaluation: nitroimidazoles (fexinidazole), currently in phase II, oxaborole DNDi-6148 and proteasome inhibitors (GNF6702

• Several drug companies (Novartis, California; and GlaxoSmithKline), and The Drugs for Neglected Diseases initiative (DNDi) have started drug discovery programs in Chagas disease;

• The Drug Discovery Unit at the University of Dundee are also running a Drug Discovery program on Chagas disease partnered with GlaxoSmithKline, Tres Cantos, Spain.

• New biomarkers for Chagas’ disease are urgently needed for the diagnosis and detection of cure/treatment efficacy.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One referee declares that they are actively involved in Chagas disease drug discovery and development and is funded by Wellcome to deliver preclinical development candidates for Chagas disease, working in partnership with GlaxoSmithKline. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose

Additional information

Funding

This work was financed in part by: the Coordenação de Aperfeiçoamento Pessoal de Nível Superior- Brasil (CAPES), Grant code 001; the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, Ed.124/2013; Ed. 15/2015); the Conselho Nacional de Desenvolvimento Científico e Tecnológico (MCTI-CNPq, Universal 14/2015) and by the Fundação Nacional de Desenvolvimento de Ensino Superior Particular - Brasil (FUNADESP).