• ert
• krabbe disease
• nanoparticles

Krabbe disease (KD) is a rare and genetic lysosomal storage disorder (LSD) caused by different mutations in the β-galactosylceramidase gene (GALC). This gene encodes for β-galactocerebrosidase, which is a lysosomal enzyme playing a crucial role in the catabolism of the myelin sheath of axons during myelin turnover. The loss of the activity of this enzyme leads to the accumulation of non-catabolized substrates and the onset of pathological features both in the central (CNS) and in the peripheral nervous system (PNS). These pathological signs include a nearly total disappearance of myelin-forming cells both in the CNS (oligodendrocytes) and in the PNS (Schwann cells) and the infiltration of the characteristic multinucleated macrophages (globoid cells). Currently, there is no cure for KD, but the available treatment options are only symptomatic and life-supporting. This issue is mainly due to the CNS-involvement and the presence of the blood-brain barrier (BBB), which precludes the passage of therapeutic agents. Thereby, the aim of this thesis is to study a brain-targeted polymeric nanoparticle-mediated ERT for the treatment of human GLD. The project foresees the carrying out of in vivo experiments on TWI mice to test whether polymeric nanovectors modified with brain-targeting peptides and loaded with GALC enzyme were able to cross the BBB and recover the enzymatic activity in the CNS.