Skreddersydd behandling av Erdheim-Chester-syndromet

Marina Ferrarini, MD (San Raffaele vitenskapelige institutt, Milano, Italia)

Lorenzo Dagna, MD (IRCCS San Raffaele Scientific Institute, Milano, Italia)

Tildelingsår: 2015
Beløp:  50 000 USD

Dr. Marina Ferrarini og dr. Lorenzo Dagna ble tildelt $50 000 for prosjektet sitt, “Skreddersydd behandling av Erdheim-Chester-syndromet”. Studien til Ferrarini og Dagna fokuserer på å forstå hvordan ondartede celler hos ECD-pasienter akkumuleres og samhandler med nærliggende normale celler for å fremme sykdommen, noe som fører til dannelse av lesjoner og svulster. Med denne forståelsen kan det være mulig å finne en behandlingsstrategi som kan avbryte prosessene og hindre sykdommen i å utvikle seg videre.

Sluttrapport

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.