Author:

Abstract:

Cystinosis is a rare inheritable multisystem storage disease which is characterized by progressive lysosomal cystine accumulation and crystal formation in all tissues throughout the body. The only specific disease-modifying treatment available is cysteamine, an amino-thiol compound which depletes the cell of cystine. Cysteamine treatment has to be monitored closely because of its narrow therapeutic window, which is currently performed by determining the leucocyte cystine level. However, this method is complex, impractical and performed in only a few specialized laboratories in the world. In this project, we aim to develop novel strategies for therapeutic monitoring of cystinosis. Current evidence points towards a role of macrophages in the pathogenesis of cystinosis, and cystine crystals as its activators. Recently in vivo reflectance confocal microscopy (RCM) of the skin in cystinosis patients identified dermal deposits specific to the disease as cystine crystals. We aim to correlate plasma chitotriosidase and IL-1Beta, IL-6 and IL-18 as markers of macrophage activation, as well as dermal and hair cystine crystal accumulation, with leucocyte cystine levels in cystinosis patients under cysteamine treatment. We will perform a multicenter longitudinal trial with serial measurement of these markers and in vivo optical coherence tomography (OCT) of skin and hair. In vitro, we will study cystinotic macrophages and macrophages of healty controls under cysteamine treatment.