Behandeling op maat voor de ziekte van Erdheim-Chester

Dr. Marina Ferrarini (Wetenschappelijk Instituut San Raffaele, Milaan, Italië)

Lorenzo Dagna, MD (Wetenschappelijk Instituut IRCCS San Raffaele, Milaan, Italië)

Jaar van toekenning: 2015
Bedrag:  50.000 USD

Dr. Marina Ferrarini en dr. Lorenzo Dagna hebben een subsidie van $50.000 ontvangen voor hun project “Behandeling op maat voor de ziekte van Erdheim-Chester”. Het onderzoek van Ferrarini en Dagna richt zich op het verkrijgen van inzicht in hoe kwaadaardige cellen bij ECD-patiënten zich ophopen en in wisselwerking staan met aangrenzende normale cellen, waardoor de ziekte wordt aangewakkerd en laesies en tumoren ontstaan. Met dit inzicht zou het mogelijk kunnen zijn om een behandelingsstrategie te ontwikkelen die deze processen kan onderbreken en zo de voortgang van de ziekte kan stoppen.

Eindrapport

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.