ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Mechanism-based combination treatment dramatically increases therapeutic efficacy in murine globoid cell leukodystrophy.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis.Frontiers in immunology · 2022Pooled it
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Metabolomic, lipidomic, and N-glycomic analyses of a human cell model of Krabbe disease reveal treatable deficits in glycosylation and serine-ceramide metabolism.bioRxiv : the preprint server for biology · 2026Article
- Sphingolipid-neutralizing molecular therapy reduces psychosine cytotoxicity in Krabbe disease.iScience · 2026Article
- Neuroimmunology in globoid cell leukodystrophy: A comprehensive review including treatments, models, and neuroimmune mechanisms underlying neuropathology.Journal of neuroimmunology · 2025Review
- The Effect of Donepezil Hydrochloride in the Twitcher Mouse Model of Krabbe Disease.Molecular neurobiology · 2024Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- 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
- Genetic spectrum and clinical features of adult leukoencephalopathies in a Chinese cohort.Annals of clinical and translational neurology · 2023Article
- Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases.Biomedicines · 2023Review
- 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
- Krabbe disease: A personal perspective and hypothesis.BioImpacts : BI · 2022Review
- A neglected neurodegenerative disease: Adult-onset globoid cell leukodystrophy.Frontiers in neuroscience · 2022Review
- Chronic lithium administration in a mouse model for Krabbe disease.JIMD reports · 2022Article
- Review
- Reduction in miR-219 expression underlies cellular pathogenesis of oligodendrocytes in a mouse model of Krabbe disease.Brain pathology (Zurich, Switzerland) · 2021Article
- Advances in the Diagnosis and Treatment of Krabbe Disease.International journal of neonatal screening · 2021Review
- Substrate reduction therapy for Krabbe disease and metachromatic leukodystrophy using a novel ceramide galactosyltransferase inhibitor.Scientific 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
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Globoid cell leukodystrophy (GLD, Krabbe disease) is a lysosomal storage disease (LSD) caused by a deficiency in galactocerebrosidase (GALC) activity. In the absence of GALC activity, the cytotoxic lipid, galactosylsphingosine (psychosine), accumulates in the CNS and peripheral nervous system. Oligodendrocytes and Schwann cells are particularly sensitive to psychosine, thus leading to a demyelinating phenotype. Although hematopoietic stem-cell transplantation provides modest benefit in both presymptomatic children and the murine model (Twitcher), there is no cure for GLD. In addition, GLD has been relatively refractory to virtually every experimental therapy attempted. Here, Twitcher mice were simultaneously treated with CNS-directed gene therapy, substrate reduction therapy, and bone marrow transplantation to target the primary pathogenic mechanism (GALC deficiency) and two secondary consequences of GALC deficiency (psychosine accumulation and neuroinflammation). Simultaneously treating multiple pathogenic targets resulted in an unprecedented increase in life span with improved motor function, persistent GALC expression, nearly normal psychosine levels, and decreased neuroinflammation. Treating the primary pathogenic mechanism and secondary targets will likely improve therapeutic efficacy for other LSDs with complex pathological and clinical presentations.
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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.