Navigating drug repurposing for Chagas disease: advances, challenges, and opportunities

Abstract

Chagas disease is a vector-borne illness caused by the protozoan parasite Trypanosoma cruzi (T. cruzi). It poses a significant public health burden, particularly in the poorest regions of Latin America. Currently, there is no available vaccine, and chemotherapy has been the traditional treatment for Chagas disease. However, the treatment options are limited to just two outdated medicines, nifurtimox and benznidazole, which have serious side effects and low efficacy, especially during the chronic phase of the disease. Collectively, this has led the World Health Organization to classify it as a neglected disease. To address this problem, new drug regimens are urgently needed. Drug repurposing, which involves the use of existing drugs already approved for the treatment of other diseases, represents an increasingly important option. This approach offers potential cost reduction in new drug discovery processes and can address pharmaceutical bottlenecks in the development of drugs for Chagas disease. In this review, we discuss the state-of-the-art of drug repurposing approaches, including combination therapy with existing drugs, to overcome the formidable challenges associated with treating Chagas disease. Organized by original therapeutic area, we describe significant recent advances, as well as the challenges in this field. In particular, we identify candidates that exhibit potential for heightened efficacy and reduced toxicity profiles with the ultimate objective of accelerating the development of new, safe, and effective treatments for Chagas disease.

Overview of Research on Leishmaniasis in Africa: Current Status, Diagnosis, Therapeutics, and Recent Advances Using By-Products of the Sargassaceae Family

“…Additionally, combination approaches involving the use of tamoxifen with meglumine antimoniate and liposomal Amp B with tretazicar have demonstrated promising results [ 62 , 63 ]. Clinical trials have assessed the combined use of AmBisome and miltefosine, revealing encouraging outcomes in immunocompromised patients co-infected with HIV and visceral leishmaniasis [ 64 , 65 ].…”

Chagas Disease across the Ages: A Historical View and Commentary on Navigating Future Challenges

“…In addition, the development of drug resistance, in conjunction with the fact that Nifurtimox and Benznidazole are considered as “obsolete” urge the development of new alternative [ 20 ]. New therapeutic options involving new or repurposed drugs [ 21 , 22 , 23 ] are urgently needed. Fexinidazole is undergoing clinical trials for the treatment of (NCT03587766), and the oxaborole DNDI-6148 has been nominated as a clinical candidate for the treatment of Chagas disease and is in phase I clinical trials (EudraCT 2018-004023-37) [ 24 ].…”

Acrylonitrile derivatives: In vitro activity and mechanism of cell death induction against Trypanosoma cruzi and Leishmania amazonensis

“…Similarly, there has been an increase in the number of studies related to the search for new therapies against Chagas disease. The use of antimicrobial peptides, such as mastoparan or crotalicidin ( Hagemann et al, 2024 ), tryptophan derivatives, such as melatonin ( Manful et al, 2024 ), or pharmacological repositioning, cholesterol-lowering treatments or antihistaminics, have shown good results in the treatment of Trypanosoma cruzi ( Porta et al, 2023 ).…”