Treatment of brain disease in the mucopolysaccharidoses

Mol Genet Metab. 2017 Dec:122S:25-34. doi: 10.1016/j.ymgme.2017.10.007. Epub 2017 Oct 16.


The mucopolysaccharidosis (MPS) disorders are a group of lysosomal storage diseases caused by lysosomal enzyme deficits that lead to glycosaminoglycan accumulation, affecting various tissues throughout the body based on the specific enzyme deficiency. These disorders are characterized by their progressive nature and a variety of somatic manifestations and neurological symptoms. There are established treatments for some MPS disorders, but these mostly alleviate somatic and non-neurological symptoms and do not cure the disease. Patients with MPS I, II, III, and VII can present with neurological manifestations such as neurocognitive decline and behavioral problems. Treatment of these neurological manifestations remains challenging due to the blood-brain barrier (BBB) that limits delivery of therapeutic agents to the central nervous system (CNS). New therapies that circumvent this barrier and target brain disease in MPS are currently under development. They primarily focus on facilitating penetration of drugs through the BBB, delivery of recombinant enzyme to the brain by gene therapy, or direct CNS administration. This review summarizes existing and potential future treatment approaches that target brain disease in MPS. The information in this review is based on current literature and presentations and discussions during a closed meeting by an international group of experts with extensive experience in managing and treating MPS.

Keywords: Blood-brain barrier; Enzyme replacement therapy; Gene therapy; Mucopolysaccharidoses; Transplantation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain / blood supply
  • Brain / cytology
  • Brain / drug effects*
  • Brain / metabolism
  • Child
  • Child Behavior / drug effects
  • Child Development / drug effects
  • Child, Preschool
  • Clinical Trials as Topic
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / therapy*
  • Congresses as Topic
  • Drug Carriers / chemistry
  • Enzyme Replacement Therapy / methods*
  • Genetic Therapy / methods
  • Glycosaminoglycans / metabolism
  • Glycosaminoglycans / toxicity
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Injections, Intraventricular
  • Injections, Spinal
  • Molecular Chaperones / therapeutic use
  • Mucopolysaccharidoses / diagnosis
  • Mucopolysaccharidoses / genetics
  • Mucopolysaccharidoses / pathology
  • Mucopolysaccharidoses / therapy*
  • Nanoparticles / chemistry
  • Recombinant Proteins / therapeutic use


  • Drug Carriers
  • Glycosaminoglycans
  • Molecular Chaperones
  • Recombinant Proteins