ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Long-Term Improvement of Neurological Signs and Metabolic Dysfunction in a Mouse Model of Krabbe's Disease after Global Gene Therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- Sphingolipid-neutralizing molecular therapy reduces psychosine cytotoxicity in Krabbe disease.iScience · 2026Article
- Impaired docking and recycling of synaptic vesicles in inherited lysosomal sphingolipidoses.Cell communication and signaling : CCS · 2025Article
- Article
- Key Challenges and Optimization Practices for Non-clinical Evaluation of AAV based Gene Therapy for Central Nervous System Disease.Pharmaceutical research · 2025Review
- Neuroimmunology in globoid cell leukodystrophy: A comprehensive review including treatments, models, and neuroimmune mechanisms underlying neuropathology.Journal of neuroimmunology · 2025Review
- Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease.Immunity · 2025Article
- STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation in lysosomal storage disorders.Molecular cell · 2025Article
- Amelioration of Inflammation and Metabolic Blockage in GALC Deficient Mice After Enzyme Replacement Therapy via Extracellular Vesicles.International journal of nanomedicine · 2025Article
- Deficiency of galactosyl-ceramidase in adult oligodendrocytes worsens disease severity during chronic experimental allergic encephalomyelitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- CD8+ T cell depletion prevents neuropathology in a mouse model of globoid cell leukodystrophy.The Journal of experimental medicine · 2023Article
- 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
- CRISPR-Cas9 Knock-In of T513M and G41S Mutations in the Murine β-Galactosyl-Ceramidase Gene Re-capitulates Early-Onset and Adult-Onset Forms of Krabbe Disease.Frontiers in molecular neuroscience · 2022Article
- New Indications for Hematopoietic Stem Cell Gene Therapy in Lysosomal Storage Disorders.Frontiers in oncology · 2022Review
- Chronic lithium administration in a mouse model for Krabbe disease.JIMD reports · 2022Article
- Review
- Advances in the Diagnosis and Treatment of Krabbe Disease.International journal of neonatal screening · 2021Review
- 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
- AAV-CNS matters turn from gray to white.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Krabbe disease: New hope for an old disease.Neuroscience letters · 2021Review
- Adeno-Associated Virus-Mediated Gene Therapy in the Mashlool,Human gene therapy · 2021Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
We report a global adeno-associated virus (AAV)9-based gene therapy protocol to deliver therapeutic galactosylceramidase (GALC), a lysosomal enzyme that is deficient in Krabbe's disease. When globally administered via intrathecal, intracranial, and intravenous injections to newborn mice affected with GALC deficiency (twitcher mice), this approach largely surpassed prior published benchmarks of survival and metabolic correction, showing long-term protection of demyelination, neuroinflammation, and motor function. Bone marrow transplantation, performed in this protocol without immunosuppressive preconditioning, added minimal benefits to the AAV9 gene therapy. Contrasting with other proposed pre-clinical therapies, these results demonstrate that achieving nearly complete correction of GALC's metabolic deficiencies across the entire nervous system via gene therapy can have a significant improvement to behavioral deficits, pathophysiological changes, and survival. These results are an important consideration for determining the safest and most effective manner for adapting gene therapy to treat this leukodystrophy in the clinic.
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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.