ArticleThe Journal of biological chemistry2011
Transport of arylsulfatase A across the blood-brain barrier in vitro.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Dose-response evaluation of intravenous gene therapy in a symptomatic mouse model of metachromatic leukodystrophy.Molecular therapy. Methods & clinical development · 2024Article
- Mucopolysaccharidoses and the blood-brain barrier.Fluids and barriers of the CNS · 2022Review
- Complete Correction of Brain and Spinal Cord Pathology in Metachromatic Leukodystrophy Mice.Frontiers in molecular neuroscience · 2021Article
- Bidirectional apical-basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening.Biotechnology and bioengineering · 2017Article
- In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016Review
- Pharmacologic manipulation of lysosomal enzyme transport across the blood-brain barrier.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016Article
- Comparison of five peptide vectors for improved brain delivery of the lysosomal enzyme arylsulfatase A.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Blood-brain barrier structure and function and the challenges for CNS drug delivery.Journal of inherited metabolic disease · 2013Review
- SyM-BBB: a microfluidic Blood Brain Barrier model.Lab on a chip · 2013Article
- Adjunctive β2-agonists reverse neuromuscular involvement in murine Pompe disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Correction of brain oligodendrocytes by AAVrh.10 intracerebral gene therapy in metachromatic leukodystrophy mice.Human gene therapy · 2012Article
- β2 Agonists enhance the efficacy of simultaneous enzyme replacement therapy in murine Pompe disease.Molecular genetics and metabolism · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enzyme replacement therapy is an option to treat lysosomal storage diseases caused by functional deficiencies of lysosomal hydrolases as intravenous injection of therapeutic enzymes can correct the catabolic defect within many organ systems. However, beneficial effects on central nervous system manifestations are very limited because the blood-brain barrier (BBB) prevents the transfer of enzyme from the circulation to the brain parenchyma. Preclinical studies in mouse models of metachromatic leukodystrophy, however, showed that arylsulfatase A (ASA) is able to cross the BBB to some extent, thus reducing lysosomal storage in brain microglial cells. The present study aims to investigate the routing of ASA across the BBB and to improve the transfer in vitro using a well established cell culture model consisting of primary porcine brain capillary endothelial cells cultured on Transwell filter inserts. Passive apical-to-basolateral ASA transfer was observed, which was not saturable up to high ASA concentrations. No active transport could be determined. The passive transendothelial transfer was, however, charge-dependent as reduced concentrations of negatively charged monosaccharides in the N-glycans of ASA or the addition of polycations increased basolateral ASA levels. Adsorptive transcytosis is therefore considered to be the major transport pathway. Partial inhibition of the transcellular ASA transfer by mannose 6-phosphate indicated a second route depending on the insulin-like growth factor II/mannose 6-phosphate receptor, MPR300. We conclude that cationization of ASA and an increase of the mannose 6-phosphate content of the enzyme may promote blood-to-brain transfer of ASA, thus leading to an improved therapeutic efficacy of enzyme replacement therapy behind the BBB.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.