ArticleAnnals of clinical and translational neurology2018
Protein production is an early biomarker for RNA-targeted therapies.
Article in Annals of clinical and translational neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
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
7 citing papers in PubMed, 9 citations in OpenAlex.
- Spatiotemporal characterization of Alzheimer disease pathology in living human brain tissue.Nature communications · 2026Article
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.Annals of clinical and translational neurology · 2023Review
- Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis.Annals of clinical and translational neurology · 2023Article
- Evaluating the efficacy of purchased antisense oligonucleotides to reduce mouse and human tauFrontiers in molecular neuroscience · 2023Article
- Antisense Oligonucleotides for the Study and Treatment of ALS.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- SILK studies - capturing the turnover of proteins linked to neurodegenerative diseases.Nature reviews. Neurology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesClinical trials for progressive neurodegenerative disorders such as Alzheimer's Disease and Amyotrophic Lateral Sclerosis have been hindered due to the absence of effective pharmacodynamics markers to assay target engagement. We tested whether measurements of new protein production would be a viable pharmacodynamics tool for RNA-targeted therapies.
methodsTransgenic animal models expressing human proteins implicated in neurodegenerative disorders - microtubule-associated protein tau (hTau) or superoxide dismutase-1 (hSOD1) - were treated with antisense oligonucleotides (ASOs) delivered to the central nervous system to target these human mRNA transcripts. Simultaneously, animals were administered
resultsASO treatment lowered hTau mRNA and protein production (measured by
interpretationMeasures of newly generated protein show earlier pharmacodynamics changes for RNA-lowering therapeutics compared with total protein concentration. Early in ASO treatment, decreases in newly generated protein are driven by changes in newly synthesized protein. Measuring new protein production in CSF may be a promising early pharmacodynamics marker for RNA-targeted therapeutics.
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.