ArticleHuman gene therapy. Clinical development2018
AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease.
Article in Human gene therapy. Clinical development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 154 citations in OpenAlex.
- Slowing late infantile Batten disease by direct brain parenchymal administration of a rh.10 adeno-associated virus expressingScience translational medicine · 2020Trial
- Reduced Effect ofNeurology. Genetics · 2026Article
- Reshaping the immune landscape: next-generation microglia-targeted therapies for Alzheimer's disease.Biological research · 2026Review
- Consequences of human genetic variations inMolecular therapy. Advances · 2026Article
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- Recent Developments in Lipid Nanoparticle-Mediated Delivery of Biotherapeutics and Gene Therapy Across the Blood-Brain Barrier.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Review
- CRISPR-Cas9 and next-generation gene editing strategies for therapeutic intervention of neurodegenerative pathways in Alzheimer's disease: a state-of-the-art review.Acta neurologica Belgica · 2026Review
- Mechanisms, Mediators, and Pharmacological Approaches Targeting Brain Cholesterol Transport in Alzheimer's Disease.Current pharmaceutical design · 2026Review
- AAV-mediated gene therapy for Alzheimer's disease: neuroprotective mechanisms and translational challenges.Frontiers in aging neuroscience · 2026Review
- The proportion of Alzheimer's disease attributable to apolipoprotein E.NPJ dementia · 2026Article
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- Flipping APOE to reverse Alzheimer's disease traits.Nature neuroscience · 2025Article
- APOE4 to APOE2 allelic switching in mice improves Alzheimer's disease-related metabolic signatures, neuropathology and cognition.Nature neuroscience · 2025Article
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Key Challenges and Optimization Practices for Non-clinical Evaluation of AAV based Gene Therapy for Central Nervous System Disease.Pharmaceutical research · 2025Review
- Stem cell and gene therapies for leukodystrophies.Molecular therapy. Methods & clinical development · 2025Review
- Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.Molecular therapy. Nucleic acids · 2025Review
44 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a progressive degenerative neurological disorder affecting nearly one in nine elderly people in the United States. Population studies have shown that an inheritance of the apolipoprotein E (APOE) variant APOE4 allele increases the risk of developing AD, whereas APOE2 homozygotes are protected from late-onset AD. It was hypothesized that expression of the "protective" APOE2 variant by genetic modification of the central nervous system (CNS) of APOE4 homozygotes could reverse or prevent progressive neurologic damage. To assess the CNS distribution and safety of APOE2 gene therapy for AD in a large-animal model, intraparenchymal, intracisternal, and intraventricular routes of delivery to the CNS of nonhuman primates of AAVrh.10hAPOE2-HA, an AAVrh.10 serotype coding for an HA-tagged human APOE2 cDNA sequence, were evaluated. To evaluate the route of delivery that achieves the widest extent of APOE2 expression in the CNS, the expression of APOE2 in the CNS was evaluated 2 months following vector administration for APOE2 DNA, mRNA, and protein. Finally, using conventional toxicology assays, the safety of the best route of delivery was assessed. The data demonstrated that while all three routes are capable of mediating ApoE2 expression in AD relevant regions, intracisternal delivery of AAVrh.10hAPOE2-HA safely mediated wide distribution of ApoE2 with the least invasive surgical intervention, thus providing the optimal strategy to deliver vector-mediated human APOE2 to the CNS.
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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.