Looking for new therapeutic alternatives for Leishmaniasis

• Grant number: 23/01641-1
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2024
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Luiz Felipe Domingues Passero
• Grantee: Luiz Felipe Domingues Passero
• Host Institution: Instituto de Biociências (IB-CLP). Universidade Estadual Paulista (UNESP). Campus Experimental do Litoral Paulista. São Vicente , SP, Brazil

Abstract

In general, neglected diseases occur in isolated areas from countries located between tropical and subtropical regions of the planet, which exhibit a huge diversity of vectors, microorganisms and reservoirs. In particular in Latin America, some infectious diseases caused by protozoal are of important epidemiological relevance, as is the case of leishmaniasis, which is caused by protoazol species of the Trypanossomatidae family and the Leishmania genus, which affect millions of people around the globe; additionally, they are important causes of death worldwide. Although significant advances have been made, there are gaps that need to be solved mainly about chemotherapy, considering that the reduced number of drugs used in therapy is not ideal, because they cause a lot of side effects in patients and are not 100% effective. To decrease the impact of current chemotherapy, our research group has been characterising molecules with leishmanicidal properties in an attempt to demonstrate that leishmaniasis therapy can be performed with alternative compounds compared to those conventionally applied. Thus, this project aims to continue the previous project, evaluating: 1) the leishmanicidal potential of extracts produced with different vegetative organs of medicinal plants (in vitro); 2) the activity of associated drugs in Leishmania sp.; 3) the efficacy of pure or associated compounds in experimental cutaneous leishmaniasis, using the topical route of treatment; 4) the efficacy of nanoformulations containing synthetic compounds, repurposed drugs associated or not in cutaneous leishmaniasis by the topic route. The immune response, analysed by quantification of reactive oxygen or nitrogen species, cytokines, or other inflammatory mediators, will be evaluated in all the cited goals, and will be performed by immunohistochemistry or flow cytometry. Finally, the development of this project will allow the development of alternative treatments for leishmaniasis compared to the currently accepted one, and this study may revolutionise the treatment of leishmaniasis for thousands of patients. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

JESUS, JESSICA ADRIANA; ARAUJO FLORES, GABRIELA VENICIA; SOUZA, DALETE CHRISTINE DA SILVA; TRISTAO, DANIELA COSTA; SERRANO, DOLORES REMEDIOS; LALATSA, AIKATERINA; LAURENTI, MARCIA DALASTRA; LAGO, JOAO HENRIQUE GHILARDI; FERRAZ, HUMBERTO GOMES; DA SILVA, ROSANA PEREIRA; et al. Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has Therapeutic Activity as a Topical Treatment in Experimental Cutaneous Leishmaniasis. MICROORGANISMS, v. 13, n. 2, p. 17-pg., 2025-02-01. (22/15834-3, 14/50315-0, 23/12447-1, 23/01641-1)

FERNANDEZ-GARCIA, RAQUEL; WALSH, DAVID; O'CONNELL, PETER; PASSERO, LUIZ FELIPE D.; DE JESUS, JESSICAA.; LAURENTI, MARCIA DALASTRA; DEA-AYUELA, MARIA AUXILIADORA; BALLESTEROS, M. PALOMA; LALATSA, AIKATERINI; BOLAS-FERNANDEZ, FRANCISCO; et al. Targeted Oral Fixed-Dose Combination of Amphotericin B-Miltefosine for Visceral Leishmaniasis. MOLECULAR PHARMACEUTICS, v. N/A, p. 12-pg., 2025-02-17. (23/01641-1)