Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficient alfa-galactosidase A activity that leads to the accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Following the introduction of enzyme replacement therapy, early diagnosis and
treatment have become essential to slow disease progression and prevent major cardiac complications. As a slowly progressive form of hypertrophic cardiomyopathy (HCM), FD resembles the phenotype of the most common sarcomeric forms, although the particular pathophysiology determines distinct clinical presentation and long-term progression.
Progress in imaging techniques has improved the diagnosis and staging of FD-related cardiac disease. Myocardial hypertrophy, inflammation and fibrosis can all contribute to disease progression and can be inferred by noninvasive imaging approaches, namely echocardiography, cardiac magnetic resonance, or positron emission tomography. However, a better correlation of imaging data with ongoing myocardial pathophysiological processes is of particular importance for a deeper comprehension of FD cardiomyopathy.
FabryPET intends to deepen the knowledge of the signalling pathways involved in cardiac remodelling of human FD by comparing the proteomics data from FD myocardial biopsies with normal tissue of heart donor biopsy samples. In this project, we also intend to characterize the process of cardiac remodelling by analyzing the profile of microRNAs related to hypertrophic cardiomyopathy and their diagnostic and prognostic value. Additionally, we intend to characterize the process of myocardial fibrosis using a new molecular imaging technic, determining its value in the diagnosis and prognosis of FD.

PI: Elisabete Martins, MD, PhD
Sub-investigator: Teresa Faria, MD, PhD