Schistosomiasis is a neglected chronic tropical disease of worldwide significance - novel therapeutic targets and drugs are required. In terms of patient numbers, after malaria, schistosomiasis is the second parasitosis in the world, being a major source of morbidity and mortality for developing countries in Africa, South America, the Caribbean, the Middle East, and Asia. More than 230 million people, 85% of who live in Africa, are infected with schistosomiasis and require treatment every year, an estimated 700 million people are at risk of infection in 76 countries where the disease is considered endemic, as their agricultural work, domestic chores, and recreational activities expose them to infested water. Since the 1970s Praziquantel (PZQ) is the drug of choice and nearly exclusively used for treatment. However, drug resistance is an increasing threat, particularly with respect to large-scale PZQ administration programs. Also the development of a vaccine still represents an elusive goal, although effort and time have been invested in this subject. In light of these facts it is commonly accepted that identification of novel relevant therapeutic targets and new drugs are urgently needed. Tools, approaches and aims: The IBCN-CNR by several decades is organized for the maintenance, development and production of Schistosomiasis parasites thus the schistosome life stages can be used for research projects. This is a unique resource in Italy for Schistosoma mansoni research and development activity. Expertise, competence and procedures to manage all schistosoma mansoni life stages from the specific snail host to infected mice are present in the Institute including skills in schistosomula preparation and culturing for biochemical, immunological and drug discovery studies. In collaboration with the IRBM Science Park (Pomezia) we will develop and validate a medium/highthroughput system (384 well microtiter plate compatibility) for reproducible specific and sensitive detection of schistosomula viability that will take advantage of the differential uptake of fluorophores by living organisms. Following a feasibily study phase, a medium to high-throughput screening will be performed with a compound collection (up to 40.000 molecules are available) including HDAC inhibitors available at the IRBM Science Park. Hits that will arise will be subsequently screened in vitro against adult parasites and finally for efficacy in a murine model of disease.
Hits identification by medium-throughput screening of a compounds collection for the discovery of novel targets and molecules involved in the Schistosoma mansoni parasite life cycle / Lalli, Cristiana. - ELETTRONICO. - (2016).
Scheda prodotto non validato
Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo
|Titolo:||Hits identification by medium-throughput screening of a compounds collection for the discovery of novel targets and molecules involved in the Schistosoma mansoni parasite life cycle|
|Data di discussione:||2016|
|Appartiene alla tipologia:||07a Tesi di Dottorato|