ArticleAnnals of neurology2012
Synergistic effects of central nervous system-directed gene therapy and bone marrow transplantation in the murine model of infantile neuronal ceroid lipofuscinosis.
Article in Annals of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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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
39 citing papers in PubMed, 78 citations in OpenAlex.
- Systemic AAV9 Gene Therapy Mitigates Neuromuscular Junction Degeneration and Muscle Atrophy in a Mouse Model of CLN1 Disease.International journal of molecular sciences · 2026Article
- Enteric nervous system degeneration in human and murine CLN3 disease, is ameliorated by gene therapy in mice.Acta neuropathologica communications · 2025Article
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- Gene therapy ameliorates neuromuscular pathology in CLN3 disease.Acta neuropathologica communications · 2025Article
- A zebrafish model of combined saposin deficiency identifies acid sphingomyelinase as a potential therapeutic target.Disease models & mechanisms · 2023Article
- An innovative hematopoietic stem cell gene therapy approach benefits CLN1 disease in the mouse model.EMBO molecular 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
- Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures.Scientific reports · 2022Article
- AAV9 Gene Therapy Increases Lifespan and Treats Pathological and Behavioral Abnormalities in a Mouse Model of CLN8-Batten Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Review
- TPP1 Delivery to Lysosomes with Extracellular Vesicles and their Enhanced Brain Distribution in the Animal Model of Batten Disease.Advanced healthcare materials · 2019Article
- Review
- Therapeutic landscape for Batten disease: current treatments and future prospects.Nature reviews. Neurology · 2019Review
- Advances in the Treatment of Neuronal Ceroid Lipofuscinosis.Expert opinion on orphan drugs · 2019Article
- Genetically Corrected iPSC-Derived Neural Stem Cell Grafts Deliver Enzyme Replacement to Affect CNS Disease in Sanfilippo B Mice.Molecular therapy. Methods & clinical development · 2018Article
- Compromised astrocyte function and survival negatively impact neurons in infantile neuronal ceroid lipofuscinosis.Acta neuropathologica communications · 2018Article
- Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons.Acta neuropathologica communications · 2017Article
- Progress toward Fulfilling the Potential of Immunomodulation in Childhood Neurodegeneration?Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Primary fibroblasts from CSPα mutation carriers recapitulate hallmarks of the adult onset neuronal ceroid lipofuscinosis.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveInfantile neuronal ceroid lipofuscinosis (INCL) is an inherited childhood neurodegenerative disorder caused by the loss of palmitoyl protein thioesterase-1 (PPT1) activity. Affected children suffer from blindness, epilepsy, motor dysfunction, cognitive decline, and premature death. The Ppt1(-/-) mouse shares the histological and clinical features of INCL. Previous single-therapy approaches using small molecule drugs, gene therapy, or neuronal stem cells resulted in partial histological correction, with minimal improvements in motor function or lifespan. Here, we combined central nervous system (CNS)-directed adeno-associated virus (AAV)2/5-mediated gene therapy with bone marrow transplantation (BMT) in the INCL mouse.
methodsAt birth, Ppt1(-/-) and wild-type mice were given either intracranial injections of AAV2/5-PPT1 or bone marrow transplantation, separately as well as in combination. To assess function, we measured rotorod performance monthly as well as lifespan. At terminal time points, we evaluated the therapeutic effects on several INCL-specific parameters, such as cortical thickness, autofluorescent accumulation, and glial activation. Finally, we determined levels of PPT1 enzyme activity and bone marrow engraftment in treated mice.
resultsAAV2/5-mediated gene therapy alone resulted in significant histological correction, improved motor function, and increased lifespan. Interestingly, the addition of BMT further increased the lifespan of treated mice and led to dramatic, sustained improvements in motor function. These data are truly striking, given that BMT alone is ineffective, yet it synergizes with CNS-directed gene therapy to dramatically increase efficacy and lifespan.
interpretationAAV2/5-mediated gene therapy in combination with BMT provides an unprecedented increase in lifespan as well as dramatic improvement on functional and histological parameters.
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