Targeting Brain Disease in Mucopolysaccharidoses

Mucopolysaccharidoses (MPSs) are a group of inherited disorders due to the deficit of the lysosomal enzymes involved in the degradation of the mucopolysaccharides, which thus accumulate within different organs, taking to a heavy progressive malfunctioning. The disorders involve most of the organ-systems and in the patients affected by MPS I, II, III and VII, also the neurological compartment may be severely affected. Many therapeutic strategies have been proposed along the years, and, following the identification of the genes underlying each disorder, in the last decade some MPSs have taken advantage on the availability of the recombinant enzymes, systemically administered to the patients. Such treatment, however, has hardly shown any effects on the CNS disease, given the inability of the enzymes to efficiently cross the blood-brain barrier. Therefore, the efforts of the last years have been focused on developing new therapeutic strategies targeting this aspect. This chapter summarizes the most relevant proposed, discussing their advantages, limitations and potential applications. Treatment of the brain disease in neuronopathic MPSs, conjugated with an early diagnosis, would represent a milestone in the improvement of patients’ and families’ life condition.

Keywords: Brain therapy, Blood-brain barrier, BBB, BBB crossing, Brain, Enzyme Replacement Therapy, ERT, Mucopolysaccharidosis, Neurological disease.