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

Treatment of brain disease in the mucopolysaccharidoses.

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Department of Paediatric and Adolescent Medicine, Helios Dr. Horst Schmidt Kliniken, Center for Rare Diseases, Wiesbaden, Germany; Department of Women's and Children's Health, University of Padova, Padova, Italy. Electronic address:
Department of Pediatrics, Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA.
Department of Pediatrics, Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Pediatrics, Program for Neurodevelopment in Rare Disorders, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Genetics, UFRGS & Medical Genetics Service, HCPA, INAGEMP, Porto Alegre, RS, Brazil.


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.


Blood-brain barrier; Enzyme replacement therapy; Gene therapy; Mucopolysaccharidoses; Transplantation

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