Translational research in Chagas disease: perspectives in nutritional therapy emerging from selenium supplementation studies as a complementary treatment

Abstract

Translational research (TR) is an interdisciplinary branch of the biomedical field that seeks to connect its three supporting pillars: basic research on the bench, the hospital beds and other health system services, and the delivery of products for the wellbeing and health of the community. Here, we review the five transition stages of the TR spectrum, registering the lessons learned during > 20 years leading to the first clinical trial designed and performed in Brazil for testing a complementary treatment for Chagas disease (CD): the selenium trial (STCC). Lessons learned were: (1) to consider all the TR spectrum since the beginning of the project; (2) to start simultaneously animal studies and translation to humans; (3) to ensure a harmonious interaction between clinical and basic research teams; (4) to include MSc and PhD students only in pre-clinical and basic studies (TR0) or vertical clinical studies using retrospective samples and data (TR1); (5) to identify potential suppliers in the national commercial market for a future final treatment since the pre-clinical stage; (6) to keep an international network of experts as permanent advisers on the project. In the whole process, some perspectives were created: a complementary clinical trial for the opened questions and the construction of a Brazilian clinical CD platform.

Diretriz da SBC sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas – 2023

“…É oportuno mencionar que o estudo da FIOCRUZ acima citado 589 incorpora-se em iniciativa abrangente de pesquisas translacionais destinadas a explorar, em caráter experimental e também clínico, hipóteses de potencial benefício com suplementação de nutrientes, como selênio, e antagonismo de fatores inflamatórios para modificar a evolução da CCDC. 593 Talvez o mérito primordial dessas investigações incipientes resida no apelo de sua hipótese fortemente embasada, fisiopatologicamente, no caráter inflamatório da CCDC e somente a pesquisa dirigida poderá responder no futuro quanto ao êxito dessas intervenções.…”

“…The previously cited study from FIOCRUZ 589 is part of a comprehensive initiative of translational research aimed at experimentally and clinically exploring hypotheses about the potential benefit of supplementation with nutrients, such as selenium, and antagonism to inflammatory factors to change the CCCD course. 593 The primordial value of these incipient investigations might reside in their strongly pathophysiology-based hypothesis on the inflammatory nature of CCCD. Only guided research will be able to provide the responses to those interventions.…”

Multi-therapeutic strategy targeting parasite and inflammation-related alterations to improve prognosis of chronic Chagas cardiomyopathy: a hypothesis-based approach*

“…(1,3) Recent findings also suggest that antioxidant therapies, also considered as nutritional approaches, as resveratrol and selenium, may be advantageous to CCC prognosis. (47,48,49) Immunoregulators as PTX, safely used in other cardiopathies, and immunological and hematological conditions, (50) may be an alternative to reeducate the immune system and control immunological unbalance in the heart tissue and systemic inflammatory profile. (18,41,43) Obviously, we should further explore other immunomodulators to ameliorate CCC, as reeducation of the immune system by therapeutic vaccines, (15) and immunoregulatory properties of other drugs as Bz, which reduces TNF expression and NF-κB signaling.…”

Clinical trials for Chagas disease: etiological and pathophysiological treatment

“…The pathogenesis of chronic CCC is not completely understood (Rassi et al, 2017;Araujo-Jorge and Ferreira, 2022). Parasite persistence and inflammation with alteration of the host's immune system can be implicated in the development of progressive heart damage caused by the infection (Coura and Borges-Pereira, 2010;Rossi et al, 2010).…”