ArticleAnnals of clinical and translational neurology2020
Adeno-associated virus serotype 1-based gene therapy for FTD caused by GRN mutations.
Article in Annals of clinical and translational neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Intra-CNS AAV9-Molecular therapy. Advances · 2026Article
- Selective neuronal restoration of progranulin does not prevent the frontotemporal dementia like-phenotype of progranulin knockout mice.Journal of neuroinflammation · 2026Article
- Shared Neuroinflammatory Mechanisms Across Dementia Types: An Integrative Review.International journal of molecular sciences · 2025Review
- Intrathalamic delivery of adeno-associated viral vector expressing progranulin as gene therapy for GRN-related frontotemporal dementia.Molecular therapy. Methods & clinical development · 2025Article
- Biodistribution of AAV1, AAV5, AAV9, and AAVDJ serotypes after intra-cisterna magna delivery in non-human primates.Molecular therapy. Methods & clinical development · 2025Article
- Analysing the effect of full-length and C-terminally truncated progranulin on proliferation, colony formation, and migration in HepG2 and U87 cells.Scientific reports · 2025Article
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Neuronal Ceroid Lipofuscinosis-Concepts, Classification, and Avenues for Therapy.CNS neuroscience & therapeutics · 2025Review
- Viral vectors in neurodegenerative diseases: immune responses and therapeutic applications.Frontiers in neurology · 2025Review
- Granulins rescue inflammation, lysosome dysfunction, lipofuscin, and neuropathology in a mouse model of progranulin deficiency.Cell reports · 2024Article
- Ependymal cells: roles in central nervous system infections and therapeutic application.Journal of neuroinflammation · 2024Review
- CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice.Nature communications · 2024Article
- Neurosurgical gene therapy for central nervous system diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Adeno-associated virus-mediated trastuzumab delivery to the central nervous system for human epidermal growth factor receptor 2+ brain metastasis.Cancer gene therapy · 2024Article
- Progranulin haploinsufficiency mediates cytoplasmic TDP-43 aggregation with lysosomal abnormalities in human microglia.Journal of neuroinflammation · 2024Article
- Identifying and Diagnosing TDP-43 Neurodegenerative Diseases in Psychiatry.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2024Review
- Antisense oligonucleotides targeting the miR-29b binding site in the GRN mRNA increase progranulin translation.The Journal of biological chemistry · 2023Article
- Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.International journal of molecular sciences · 2023Review
- Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease.Human gene therapy · 2023Article
- AAV-iScience · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveDominant loss-of-function mutations in the gene encoding the lysosomal protein, progranulin, cause 5-10% of frontotemporal dementia cases. As progranulin undergoes secretion and endocytosis, a small number of progranulin-expressing cells can potentially supply the protein to the entire central nervous system. Thus, gene therapy is a promising treatment approach.
methodsWe evaluated adeno-associated viral vector administration into the cerebrospinal fluid as a minimally invasive approach to deliver the granulin gene to the central nervous system in a murine disease model and nonhuman primates.
resultsIn progranulin-deficient mice, vector delivery into the lateral cerebral ventricles increased progranulin levels in the cerebrospinal fluid and normalized histological and biochemical markers of progranulin deficiency. A single vector injection into the cisterna magna of nonhuman primates achieved CSF progranulin concentrations up to 40-fold higher than those of normal human subjects and exceeded CSF progranulin levels of successfully treated mice. Animals treated with an adeno-associated virus serotype 1 vector exhibited progranulin expression fivefold higher than those treated with an AAV5 vector or the AAV9 variant, AAVhu68, apparently due to remarkably efficient transduction of ependymal cells. Progranulin expression mediated by adeno-associated viral vectors was well tolerated in nonhuman primates with no evidence of dose-limiting toxicity, even at vector doses that induced supraphysiologic progranulin expression.
interpretationThese findings support the development of AAV1-based gene therapy for frontotemporal dementia caused by progranulin deficiency.
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