Current and Emerging Therapies for Mucopolysaccharidoses.

ABSTRACT

Mucopolysaccharidoses (MPSs) are caused by deficiencies of specific lysosomal enzymes that affect the degradation of mucopolysaccharides or glycosaminoglycans (GAGs). Enzyme replacement therapies are available for an increasing number of MPSs since more than 15 years. Together with hematopoietic stem cell transplantation, these enzyme therapies are currently the gold standard of causal treatment in MPS. Both treatments can improve symptoms and prognosis, but they do not cure these severe conditions. The limitations of intravenous enzyme replacement and cell therapy can be summarized as the development of immune reactions against the therapeutic molecules/cells and failure to restore enduring and sufficient drug exposures in all relevant tissues. Thus innovative approaches include small molecules and encapsulated cells that do not induce immune reactions, gene therapy approaches that aim for sustained enzyme expression, and new enzymes that are able to penetrate barriers to drug distribution like the blood-brain barrier. This chapter provides an update on the state of development of these new therapies and highlights current challenges.