ArticleAnalytical biochemistry2013
A high-throughput screening assay using Krabbe disease patient cells.
Article in Analytical biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Chr:17q21.31 locus risk haplotype H1 susceptibility to ferroptosis is mediated by endolysosomal pathway.Cell death & disease · 2025Article
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- Activation of mitochondrial TRAP1 stimulates mitochondria-lysosome crosstalk and correction of lysosomal dysfunction.iScience · 2022Article
- Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes.Stem cell reports · 2021Article
- New therapeutic approaches for Krabbe disease: The potential of pharmacological chaperones.Journal of neuroscience research · 2016Review
- Cell-based high-throughput screening identifies galactocerebrosidase enhancers as potential small-molecule therapies for Krabbe's disease.Journal of neuroscience research · 2016Article
- Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants.Traffic (Copenhagen, Denmark) · 2016Article
- Disease models for the development of therapies for lysosomal storage diseases.Annals of the New York Academy of Sciences · 2016Review
- Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis.Orphanet journal of rare diseases · 2016Review
- Altered Trafficking and Processing of GALC Mutants Correlates with Globoid Cell Leukodystrophy Severity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Article
- Chaperone therapy for Krabbe disease: potential for late-onset GALC mutations.Journal of human genetics · 2015Article
- Emerging treatments for pediatric leukodystrophies.Pediatric clinics of North America · 2015Review
- Azasugar inhibitors as pharmacological chaperones for Krabbe disease.Chemical science · 2015Article
- Disease specific therapies in leukodystrophies and leukoencephalopathies.Molecular genetics and metabolism · 2015Article
- Structural snapshots illustrate the catalytic cycle of β-galactocerebrosidase, the defective enzyme in Krabbe disease.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Developing therapeutic approaches for metachromatic leukodystrophy.Drug design, development and therapy · 2013Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
Globoid cell leukodystrophy (GLD) or Krabbe disease is a lysosomal disease caused by β-galactocerebrosidase (GALC) deficiency resulting in a rapidly progressive neurodegenerative disorder. Unfortunately, the only available treatment is hematopoietic bone marrow transplantation, which prevents its fulminant manifestation but without treating further neurological manifestations. Here, we describe the development of a cellular high-throughput screening (HTS) assay using GLD patient fibroblasts to screen for small molecules that enhance the residual mutant GALC enzymatic activity. Small molecules have substantial therapeutic potential in GLD because they are more prone to cross the blood-brain barrier, reaching the neuronal affected cells. The transformation of primary skin fibroblasts with SV40 large T antigen has been shown to maintain the biochemical characteristics of the GLD cells and generates sufficient cells for the HTS. Using a specific fluorescent substrate, residual GALC activity from an SV40-transformed GLD patient fibroblast was measurable in high-density microplates. The pilot quantitative HTS against a small compound collection showed robust statistics. The small molecules that showed active concentration-response curves were further studied in primary GLD fibroblasts. This cell-based HTS assay demonstrates the feasibility of employing live GLD patient cells to identify therapeutic agents that can potentially be used for the treatment of this progressive neurodegenerative disease.
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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.