ArticleHuman molecular genetics2015
Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- Chimeric enzymes enhance treatment potential for globoid cell leukodystrophy through hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Advanced biomaterials for rare Krabbe disease: galactocerebrosidase scaffolds in demyelinating lesions.Annals of medicine and surgery (2012) · 2025Article
- Combination HSCT and intravenous AAV-mediated gene therapy in a canine model proves pivotal for translation of Krabbe disease therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Untargeted Lipidomic Approach for Studying Different Nervous System Tissues of the Murine Model of Krabbe Disease.Biomolecules · 2023Article
- Article
- Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Therapeutic advantages of combined gene/cell therapy strategies in a murine model of GM2 gangliosidosis.Molecular therapy. Methods & clinical development · 2022Article
- Chronic lithium administration in a mouse model for Krabbe disease.JIMD reports · 2022Article
- Krabbe disease: A personal perspective and hypothesis.BioImpacts : BI · 2022Review
- Review
- Advances in the Diagnosis and Treatment of Krabbe Disease.International journal of neonatal screening · 2021Review
- Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes.Stem cell reports · 2021Article
- Waning efficacy in a long-term AAV-mediated gene therapy study in the murine model of Krabbe disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Enhanced Efficacy and Increased Long-Term Toxicity of CNS-Directed, AAV-Based Combination Therapy for Krabbe Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Review
- Can early treatment of twitcher mice with high dose AAVrh10-GALC eliminate the need for BMT?BioImpacts : BI · 2021Article
- Delivery Platforms for CRISPR/Cas9 Genome Editing of Glial Cells in the Central Nervous System.Frontiers in genome editing · 2021Review
- Brainstem development requires galactosylceramidase and is critical for pathogenesis in a model of Krabbe disease.Nature communications · 2020Article
- POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches.Frontiers in cellular neuroscience · 2020Article
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing dramatic extension of lifespan and global clinical-pathological rescue in a relevant GLD murine model. We show that timely and long-lasting delivery of functional GALC in affected tissues ensured by the exclusive complementary mode of action of the treatments underlies the outstanding benefit. In particular, the contribution of neural stem cell transplantation and IC GT during the early asymptomatic stage of the disease is instrumental to enhance long-term advantage upon BMT. We clarify the input of central nervous system, peripheral nervous system and periphery to the disease, and the relative contribution of treatments to the final therapeutic outcome, with important implications for treatment strategies to be tried in human patients. This study gives proof-of-concept of efficacy, tolerability and clinical relevance of the combined gene/cell therapies proposed here, which may constitute a feasible and effective therapeutic opportunity for children affected by GLD.
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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.