Work Package 3

Title of Work Package: Molecular biomarkers for disease progression and monitoring therapy

Objectives: WP3 will concentrate on discovery and validation of biomarkers to monitor disease progression and therapeutic effects. We will use biomaterial from patients available through our registry (WP1) and our clinical study (WP4). Blood samples will be collected at intervals for RNA extraction and serum preparation. Biomaterials (including blood, serum, urine and tissues) derived from animal models will be also used to establish transcriptomic and metabolomic profiles under basal conditions and to monitor the effects of treatments as described in WP5.

Tasks

• Indentification of biomarkers for PKAN; biomaterials derived from genetically characterized PKAN patients and a matched cohort of controls will be used to define a signature of the disease to be used as a baseline to monitor the effects of drug treatment.
• Validation of results obtained with transcriptomic and metabolomic approaches; potentially relevant transcripts and metabolites will be further validated with independent methods.
• Evaluation of specific biomarkers during therapy; biomarkers indentified in the previous tasks will be used to follow-up on patients under Deferiprone therapy at several time intervals. This will help clairfy the potential benefit of the treament and to establish if therapy adjustments are needed.