ArticleEMBO molecular medicine2016
Pervasive supply of therapeutic lysosomal enzymes in the CNS of normal and Krabbe-affected non-human primates by intracerebral lentiviral gene therapy.
Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 53 citations in OpenAlex.
- Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.Lancet (London, England) · 2022Trial
- 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
- Article
- Neurosurgical gene therapy for central nervous system diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Biomaterial-based gene therapy.MedComm · 2023Review
- Intracerebral lentiviral ABCD1 gene therapy in an early disease onset ALD mouse model.Gene therapy · 2023Article
- Review
- Therapeutic advantages of combined gene/cell therapy strategies in a murine model of GM2 gangliosidosis.Molecular therapy. Methods & clinical development · 2022Article
- Gene Therapy Developments for Pompe Disease.Biomedicines · 2022Review
- Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes.Stem cell reports · 2021Article
- Krabbe disease: New hope for an old disease.Neuroscience letters · 2021Review
- Gene therapy using haematopoietic stem and progenitor cells.Nature reviews. Genetics · 2021Review
- Functionalized Silica Star-Shaped Nanoparticles and Human Mesenchymal Stem Cells: An In Vitro Model.Nanomaterials (Basel, Switzerland) · 2021Article
- Update on Clinical Ex Vivo Hematopoietic Stem Cell Gene Therapy for Inherited Monogenic Diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- 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
- Delivery Platforms for CRISPR/Cas9 Genome Editing of Glial Cells in the Central Nervous System.Frontiers in genome editing · 2021Review
- Review
- Krabbe Disease: Prospects of Finding a Cure Using AAV Gene Therapy.Frontiers in medicine · 2021Review
- Unpatterned Bioactive Poly(Butylene 1,4-Cyclohexanedicarboxylate)-Based Film Fast Induced Neuronal-Like Differentiation of Human Bone Marrow-Mesenchymal Stem Cells.International journal of molecular sciences · 2020Article
- Identification of a missense ARSA mutation in metachromatic leukodystrophy and its potential pathogenic mechanism.Molecular genetics & genomic medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
Metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD or Krabbe disease) are severe neurodegenerative lysosomal storage diseases (LSD) caused by arylsulfatase A (ARSA) and galactosylceramidase (GALC) deficiency, respectively. Our previous studies established lentiviral gene therapy (GT) as a rapid and effective intervention to provide pervasive supply of therapeutic lysosomal enzymes in CNS tissues of MLD and GLD mice. Here, we investigated whether this strategy is similarly effective in juvenile non-human primates (NHP). To provide proof of principle for tolerability and biological efficacy of the strategy, we established a comprehensive study in normal NHP delivering a clinically relevant lentiviral vector encoding for the human ARSA transgene. Then, we injected a lentiviral vector coding for the human GALC transgene in Krabbe-affected rhesus macaques, evaluating for the first time the therapeutic potential of lentiviral GT in this unique LSD model. We showed favorable safety profile and consistent pattern of LV transduction and enzyme biodistribution in the two models, supporting the robustness of the proposed GT platform. We documented moderate inflammation at the injection sites, mild immune response to vector particles in few treated animals, no indication of immune response against transgenic products, and no molecular evidence of insertional genotoxicity. Efficient gene transfer in neurons, astrocytes, and oligodendrocytes close to the injection sites resulted in robust production and extensive spreading of transgenic enzymes in the whole CNS and in CSF, leading to supraphysiological ARSA activity in normal NHP and close to physiological GALC activity in the Krabbe NHP, in which biological efficacy was associated with preliminary indication of therapeutic benefit. These results support the rationale for the clinical translation of intracerebral lentiviral GT to address CNS pathology in MLD, GLD, and other neurodegenerative LSD.
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.