Treatment of brain disease in the mucopolysaccharidoses

TY - JOUR

T1 - Treatment of brain disease in the mucopolysaccharidoses

AU - Scarpa, Maurizio

AU - orchard, paul

AU - Schulz, Angela

AU - Dickson, Patrizia I

AU - Haskins, Mark E

AU - Escolar, Maria L

AU - Giugliani, Roberto

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2017/10/16

Y1 - 2017/10/16

N2 - 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.

AB - 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.

KW - Journal Article

KW - Review

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ymgme.2017.10.007

DO - 10.1016/j.ymgme.2017.10.007

M3 - SCORING: Review article

C2 - 29153844

VL - 122S

SP - 25

EP - 34

JO - MOL GENET METAB

JF - MOL GENET METAB

SN - 1096-7192

ER -