ArticleThe Journal of clinical investigation2022
AAV9/MFSD8 gene therapy is effective in preclinical models of neuronal ceroid lipofuscinosis type 7 disease.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- Design and initial characterization of a novel mini-promoter for gene therapies targeting the central nervous system.Molecular therapy. Advances · 2026Article
- Connectomic and behavioural alterations in creatine transporter deficiency are partially normalized by gene therapy.Brain : a journal of neurology · 2026Article
- A Head-to-Head Comparison of AAV9 Biodistribution in Mice: Routes of Administration and Age Dependence.Genes · 2026Article
- Non-targeted Metabolomics Reveals the Potential Role of MFSD8 in Metabolism in Human Endothelial Cells.Molecular biotechnology · 2026Article
- Prognostic value of fatty acid metabolism-related signature and integrated analysis of the immune microenvironment in multiple myeloma.BMC cancer · 2025Article
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- Improved AAV9-based gene therapy design forMolecular therapy. Methods & clinical development · 2025Article
- Trojan horse-inspired spatiotemporal strategy augments cartilage regeneration by enhancing mitochondrial energy production.Innovation (Cambridge (Mass.)) · 2025Article
- IMPC impact on preclinical mouse models.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Expression and distribution of rAAV9 intrathecally administered in juvenile to adolescent mice.Gene therapy · 2025Article
- STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation in lysosomal storage disorders.Molecular cell · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Gene-replacement therapy in neurodevelopmental disorders: progress and challenges.The Journal of clinical investigation · 2025Review
- Neuronal Ceroid Lipofuscinosis-Concepts, Classification, and Avenues for Therapy.CNS neuroscience & therapeutics · 2025Review
- Preclinical use of a clinically-relevant scAAV9/SUMF1 vector for the treatment of multiple sulfatase deficiency.Communications medicine · 2025Article
- Maculopathy and adult-onset ataxia in patients with biallelic MFSD8 variants.Molecular genetics & genomic medicine · 2024Article
- Intrathecal delivery of a bicistronic AAV9 vector expressing β-hexosaminidase A corrects Sandhoff disease in a murine model: A dosage study.Molecular therapy. Methods & clinical development · 2024Article
- AAV-based in vivo gene therapy for neurological disorders.Nature reviews. Drug discovery · 2023Review
- Biochemical Correction of GM2 Ganglioside Accumulation in AB-Variant GM2 Gangliosidosis.International journal of molecular sciences · 2023Article
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7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal ceroid lipofuscinosis type 7 (CLN7) disease is a lysosomal storage disease caused by mutations in the facilitator superfamily domain containing 8 (MFSD8) gene, which encodes a membrane-bound lysosomal protein, MFSD8. To test the effectiveness and safety of adeno-associated viral (AAV) gene therapy, an in vitro study demonstrated that AAV2/MFSD8 dose dependently rescued lysosomal function in fibroblasts from a CLN7 patient. An in vivo efficacy study using intrathecal administration of AAV9/MFSD8 to Mfsd8- /- mice at P7-P10 or P120 with high or low dose led to clear age- and dose-dependent effects. A high dose of AAV9/MFSD8 at P7-P10 resulted in widespread MFSD8 mRNA expression, tendency of amelioration of subunit c of mitochondrial ATP synthase accumulation and glial fibrillary acidic protein immunoreactivity, normalization of impaired behaviors, doubled median life span, and extended normal body weight gain. In vivo safety studies in rodents concluded that intrathecal administration of AAV9/MFSD8 was safe and well tolerated. In summary, these results demonstrated that the AAV9/MFSD8 vector is both effective and safe in preclinical models.
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