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.
