Lysosomal storage diseases (LSDs) are a group of rare genetic multisystemic disorders, resulting in deficient
lysosomal activity. These pathologies are characterized by progressive accumulation of storage material within the
lysosomes, ultimately leading to organ dysfunctions. LSDs patient’s clinical outcomes have significantly improved, since
the advent of enzyme replacement therapy (ERT). ERT is approved worldwide for 6 LSDs: Gaucher disease, Fabry
disease, Mucopolysaccharidosis types I, II, and VI, and Pompe disease. The efficacy and safety of ERT for LSDs has been
confirmed by extensive clinical trials, however therapy with infused protein is life-long and disease progression is still
observed in treated patients. Obstacles to successful ERT, such as immune reactions against the infused enzyme,
miss-targeting of recombinant enzymes, and difficult delivery to crucial tissues (i.e. brain and bone), determine the need
for further research, in order to ameliorate therapeutic strategies. Viral gene therapy, stem cell based therapy, pharmacological
chaperones and could be considered essential tools for future improvement of recombinant enzyme trafficking and
targeting. This review will discuss recent patents and new strategic approaches for enzyme delivery to highlight the most
relevant aspects, concerning next generation LSDs treatment.
Keywords: Enzyme replacement therapy, Fabry disease, Gaucher disease, gene therapy, hematopoietic stem cells transplantation,
lysosomal storage diseases, pharmacological chaperons, substrate reduction therapy.
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