Treatment of brain disease in the mucopolysaccharidoses

Maurizio Scarpa, Paul J Orchard, Angela Schulz, Patricia I. Dickson, Mark E. Haskins, Maria L. Escolar, Roberto Giugliani

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalMolecular Genetics and Metabolism
Volume122
DOIs
StatePublished - Dec 1 2017

Fingerprint

Mucopolysaccharidoses
Brain Diseases
Brain
Neurologic Manifestations
Neurology
Blood-Brain Barrier
Enzymes
Gene therapy
Mucopolysaccharidosis II
Central Nervous System Agents
Mucopolysaccharidosis I
Lysosomal Storage Diseases
Therapeutics
Glycosaminoglycans
Group Processes
Genetic Therapy
Tissue
Central Nervous System
Pharmaceutical Preparations

Keywords

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

Cite this

Scarpa, M., Orchard, P. J., Schulz, A., Dickson, P. I., Haskins, M. E., Escolar, M. L., & Giugliani, R. (2017). Treatment of brain disease in the mucopolysaccharidoses. Molecular Genetics and Metabolism, 122, 25-34. https://doi.org/10.1016/j.ymgme.2017.10.007

Treatment of brain disease in the mucopolysaccharidoses. / Scarpa, Maurizio; Orchard, Paul J; Schulz, Angela; Dickson, Patricia I.; Haskins, Mark E.; Escolar, Maria L.; Giugliani, Roberto.

In: Molecular Genetics and Metabolism, Vol. 122, 01.12.2017, p. 25-34.

Research output: Contribution to journalReview article

Scarpa, M, Orchard, PJ, Schulz, A, Dickson, PI, Haskins, ME, Escolar, ML & Giugliani, R 2017, 'Treatment of brain disease in the mucopolysaccharidoses', Molecular Genetics and Metabolism, vol. 122, pp. 25-34. https://doi.org/10.1016/j.ymgme.2017.10.007
Scarpa, Maurizio ; Orchard, Paul J ; Schulz, Angela ; Dickson, Patricia I. ; Haskins, Mark E. ; Escolar, Maria L. ; Giugliani, Roberto. / Treatment of brain disease in the mucopolysaccharidoses. In: Molecular Genetics and Metabolism. 2017 ; Vol. 122. pp. 25-34.
@article{926ed9b475174ec6824d2ddef74af7f1,
title = "Treatment of brain disease in the mucopolysaccharidoses",
abstract = "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",
author = "Maurizio Scarpa and Orchard, {Paul J} and Angela Schulz and Dickson, {Patricia I.} and Haskins, {Mark E.} and Escolar, {Maria L.} and Roberto Giugliani",
year = "2017",
month = "12",
day = "1",
doi = "10.1016/j.ymgme.2017.10.007",
language = "English (US)",
volume = "122",
pages = "25--34",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Treatment of brain disease in the mucopolysaccharidoses

AU - Scarpa, Maurizio

AU - Orchard, Paul J

AU - Schulz, Angela

AU - Dickson, Patricia I.

AU - Haskins, Mark E.

AU - Escolar, Maria L.

AU - Giugliani, Roberto

PY - 2017/12/1

Y1 - 2017/12/1

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 - Blood-brain barrier

KW - Enzyme replacement therapy

KW - Gene therapy

KW - Mucopolysaccharidoses

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=85033789412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033789412&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2017.10.007

DO - 10.1016/j.ymgme.2017.10.007

M3 - Review article

VL - 122

SP - 25

EP - 34

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

ER -