ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Targeting Amyloid-β Precursor Protein, APP, Splicing with Antisense Oligonucleotides Reduces Toxic Amyloid-β Production.
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 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Safety considerations of gene-based therapies for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- A splice-switching antisense oligonucleotide approach for pediatric genetic epilepsies.bioRxiv : the preprint server for biology · 2025Article
- Therapeutic targeting of alternative splicing caused by a lethal noncoding structural variant in X-linked dystonia parkinsonism.medRxiv : the preprint server for health sciences · 2025Article
- Therapeutic Advances in Targeting the Amyloid-β Pathway for Alzheimer's Disease.Brain sciences · 2025Review
- APP Gene-based Strategies to Combat Alzheimer's Disease in Down Syndrome.Current genomics · 2025Article
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- SPLICER: a highly efficient base editing toolbox that enables in vivo therapeutic exon skipping.Nature communications · 2024Article
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
- Therapeutic potential of APP antisense oligonucleotides for Alzheimer's disease and down syndrome-related Alzheimer's disease.Molecular neurodegeneration · 2024Article
- APP antisense oligonucleotides reduce amyloid-β aggregation and rescue endolysosomal dysfunction in Alzheimer's disease.Brain : a journal of neurology · 2024Article
- APP dyshomeostasis in the pathogenesis of Alzheimer's disease: implications for current drug targets.Alzheimer's research & therapy · 2024Review
- Unraveling the Genetic Landscape of Neurological Disorders: Insights into Pathogenesis, Techniques for Variant Identification, and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Splice-switching antisense oligonucleotides for pediatric neurological disorders.Frontiers in molecular neuroscience · 2024Review
- The epigenetic modification of DNA methylation in neurological diseases.Frontiers in immunology · 2024Review
- Alternative splicing in neurodegenerative disease and the promise of RNA therapies.Nature reviews. Neuroscience · 2023Review
- Tip60's Novel RNA-Binding Function Modulates Alternative Splicing of Pre-mRNA Targets Implicated in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Proteinopathies: Deciphering Physiology and Mechanisms to Develop Effective Therapies for Neurodegenerative Diseases.Molecular neurobiology · 2022Review
- Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders.Journal of personalized medicine · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Alterations in amyloid beta precursor protein (APP) have been implicated in cognitive decline in Alzheimer's disease (AD), which is accelerated in Down syndrome/Trisomy 21 (DS/TS21), likely due to the extra copy of the APP gene, located on chromosome 21. Proteolytic cleavage of APP generates amyloid-β (Aβ) peptide, the primary component of senile plaques associated with AD. Reducing Aβ production is predicted to lower plaque burden and mitigate AD symptoms. Here, we designed a splice-switching antisense oligonucleotide (SSO) that causes skipping of the APP exon that encodes proteolytic cleavage sites required for Aβ peptide production. The SSO induced exon skipping in Down syndrome cell lines, resulting in a reduction of Aβ. Treatment of mice with the SSO resulted in widespread distribution in the brain accompanied by APP exon skipping and a reduction of Aβ. Overall, we show that an alternatively spliced isoform of APP encodes a cleavage-incompetent protein that does not produce Aβ peptide and that promoting the production of this isoform with an SSO can reduce Aβ in vivo. These findings demonstrate the utility of using SSOs to induce a spliced isoform of APP to reduce Aβ as a potential approach for treating AD.
Indexed as
Identifiers
What OpenQuestion holds
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.