Adaptation du traitement de la maladie d'Erdheim-Chester

Marina Ferrarini, docteur en médecine (Institut scientifique San Raffaele, Milan, Italie)

Dr Lorenzo Dagna (Institut scientifique IRCCS San Raffaele, Milan, Italie)

Année d'attribution : 2015
Montant :  50 000 USD

Le Dr Marina Ferrarini et le Dr Lorenzo Dagna se sont vu attribuer une subvention de $50 000 pour leur projet intitulé “ Personnalisation du traitement de la maladie d’Erdheim-Chester ”. L'étude de Marina Ferrarini et Lorenzo Dagna vise à comprendre comment les cellules malignes chez les patients atteints de la maladie d'Erdheim-Chester s'accumulent et interagissent avec les cellules saines voisines pour alimenter la maladie, entraînant la formation de lésions et de tumeurs. Grâce à ces connaissances, il pourrait être possible de mettre au point une stratégie thérapeutique capable d'interrompre ces processus et d'enrayer la progression de la maladie.

Rapport final

Our study focuses on a better understanding of the pathogenic events operating inside ECD lesions, as well as the mechanisms exerted by selected drugs/new molecules on mutated histiocytes. This is expected to result in the discovery of novel strategies providing ECD patients with treatments that are more effective and with fewer side effects than those currently available. So far, we have identified molecules and pathways that may have a key role in disease progression; we plan to investigate how these molecules act to fuel the disease and also test the efficacy of potentially available inhibitors. In order to validate these findings and improve treatment for ECD patients, we are also taking advantage of state-of-the-art bioreactor technology. The bioreactor, originally developed by NASA spatial research, works under conditions of simulated microgravity, allowing the tissue to remain viable during culture and offering the unprecedented possibility to test and compare the effectiveness of treatments. We were able to apply this technology, which we have already exploited for other diseases, also to ECD tissues. We have collected information on the mechanisms exerted by available drugs, particularly kinase inhibitors, on ECD lesions, unveiling new putative therapeutic targets, in particular metabolic pathways, that can be further exploited to design new combination therapies. Finally, we have identified Chromogranin A, a pro-hormone associated with inflammation and heart failure, as a possible marker of cardiac disease also in ECD. This molecule can be detected in plasma samples and can be potentially used as a novel non-invasive procedure to monitor cardiovascular involvement and response to treatment in ECD patients.