NDTND

Development of new diagnostic and treatment options for helminthic neglected diseases

PARTNERS

• University of Buenos Aires and National Council of Scientific and Technological Research, Argentina. (Betina Córsico, Mara Rosenzvit – Project coordinator)
• Istituto Superiore di Sanità, Italy. (Adriano Casulli)
• Facultad de Ciencias, UdelaR, Uruguay. (Estela Castillo, Uriel Koziol)
• University of Würzburg, Germany. (Klaus Brehm)
• San Matteo Hospital Foundation, Italy. (Enrico Brunetti, Mara Mariconti)

Timing: 2017-2022. Funder: European Commission (ERANet-LAC 2) and participating Ministries of Health (G.A. ELAC2015/T08-0544). Total cost: 945.083 €.

NDTND aims at developing new therapeutic and diagnostic tools to contribute to the control of neglected diseases caused by helminth parasites, such as cystic (CE) and alveolar (AE) echinococcosis. We propose a novel approach based on distinct biological and metabolic aspects of helminth parasites, considering in particular parasite specific a) lipid binding proteins (LBPs) and b) microRNAs (miRNAs). We will also assess their cellular expression in order to prioritize targets that are widely expressed, including key stem cell population. The uniqueness/divergence of several miRNAs and the ability to be detected in biological fluids also makes them potential new specific biomarkers. Ultrasound (US) surveys and sera collection from humans affected by CE will be performed in order to link the potentially new biomarkers in the stage specific approach according to WHOIWGE. In addition, US surveys will provide a rapid impact on the health system of the rural populations involved in the study. Sera from AE patients are available. We will evaluate specific parasite molecules as new therapeutic/diagnosis targets using bioinformatics, molecular biology, biochemistry and biophysical methods integrated with relevant clinical and epidemiological information. The expected outcomes of the project are the development of new compounds that bind and inhibit essential and unique molecules of these parasites and to find new detection tools, to improve the status of both treatment and early diagnosis of these complex and neglected diseases.

PUBLICATIONS

• Grecco A, Macchiaroli N, Pérez MG, Casulli A, Cucher MA, Rosenzvit MC. microRNA silencing in a whole worm cestode model provides insight into miR-71 function. International Journal of Parasitology. 2023 Sep 10: S0020-7519(23)00187-X
• Macchiaroli N, Preza M, Pérez MG, Kamenetzky L, Cucher M, Koziol U, Castillo E, Berriman M, Brehm K, Rosenzvit MC. Expression profiling of Echinococcus multilocularis miRNAs throughout metacestode development in vitro. PLoS Neglected Tropical Diseases. 2021 Mar 22;15(3):e0009297
• Dezsényi B, Dubóczki Z, Strausz T, Csulak E, Czoma V, Káposztás Z, Fehérvári M, Somorácz Á, Csilek A, Oláh A, Almási K, Patonai A, Görög D, Széll Z, Tolnai Z, Sréter T, Danka J, Auer H, Grüner B, Barth TFE, Casulli A. Emerging human alveolar echinococcosis in Hungary (2003-2018): a retrospective case series analysis from a multi-centre study. BMC Infectious Diseases. 2021 Feb 10;21(1):168.
• Ancarola ME, Lichtenstein G, Herbig J, Holroyd N, Mariconti M, Brunetti E, Berriman M, Albrecht K, Marcilla A, Rosenzvit MC, Kamenetzky L, Brehm K, Cucher M. Extracellular non-coding RNA signatures of the metacestode stage of Echinococcus multilocularis. PLoS Neglected Tropical Diseases. 2020 Nov 30;14(11):e0008890
• Pórfido JL, Herz M, Kiss F, Kamenetzky L, Brehm K, Rosenzvit MC, Córsico B, Franchini GR. Fatty acid-binding proteins in Echinococcus spp.: the family has grown [Abstract]. Parasitology Research. 2020 Apr;119(4):1401-1408
• Bélgamo JA, Alberca LN, Pórfido JL, Romero FNC, Rodriguez S, Talevi A, Córsico B, Franchini GR. Application of target repositioning and in silico screening to exploit fatty acid binding proteins (FABPs) from Echinococcus multilocularis as possible drug targets. [Abstract]. Journal of Computed Aided Molecular Design. 2020 Dec;34(12):1275-1288
• Manciulli T, Serraino R, D'Alessandro GL, Cattaneo L, Mariconti M, Vola A, Taccari F, Narra R, De Vito G, Trecarichi EM, Mazzitelli M, Matera G, Casulli A, Marascio N, Brunetti E, Tamarozzi F, Torti C. Evidence of Low Prevalence of Cystic Echinococcosis in the Catanzaro Province, Calabria Region, Italy. [Abstract]. American Journal of Tropical Medicine and Hygiene. 2020 Nov;103(5):1951-1954
• Pérez MG, Spiliotis M, Rego N, Macchiaroli N, Kamenetzky L, Holroyd N, Cucher MA, Brehm K, Rosenzvit MC. Deciphering the role of miR-71 in Echinococcus multilocularis early development in vitro. PLoS Neglected Tropical Diseases. 2019 Dec 27;13(12):e0007932
• Bakhtiar NM, Akbarzadeh A, Casulli A, Mahami-Oskouei M, Ahmadpour E, Nami S, Rostami A, Spotin A. Therapeutic efficacy of nanocompounds in the treatment of cystic and alveolar echinococcoses: challenges and future prospects.[Abstract]. Parasitology Research. 2019 Sep;118(9):2455-2466
• Laurimäe T, Kinkar L, Romig T, Umhang G, Casulli A, Omer RA, Sharbatkhori M, Mirhendi H, Ponce-Gordo F, Lazzarini LE, Soriano SV, Varcasia A, Rostami-Nejad M, Andresiuk V, Maravilla P, González LM, Dybicz M, Gawor J, Šarkūnas M, Šnábel V, Kuzmina T, Kia EB, Saarma U. Analysis of nad2 and nad5 enables reliable identification of genotypes G6 and G7 within the species complex Echinococcus granulosus sensu lato. [Abstract]. Infection, Genetics and Evolution. 2019 Oct;74:103941
• Casulli A, Siles-Lucas M, Tamarozzi F. Echinococcus granulosus sensu lato. [Abstract]. Trends in Parasitology. 2019 Aug;35(8):663-664
• Casulli A, Barth TFE, Tamarozzi F. Echinococcus multilocularis. [Abstract]. Trends in Parasitology. 2019 Sep;35(9):738-739