ArticleAnnals of neurology2023
Antisense Oligonucleotide Silencing Reverses Abnormal Neurochemistry in Spinocerebellar Ataxia 3 Mice.
Article in Annals of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 28 citations in OpenAlex.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Translational Paradox of Triplet Repeat Expansion Disorders: Synthesizing Clinical Trial Failures to Guide Future Therapeutics.Clinical pharmacology and therapeutics · 2026Review
- MRI end-points for clinical trials in ataxias: recommendations from the Ataxia Global Initiative MRI Biomarkers Working Group.Nature reviews. Neurology · 2026Review
- Rad23b exacerbates pathological aggregates through disrupting proteasome functions in Spinocerebellar ataxia type 3.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Relationship of subclinical lung injury to chronic airway inflammation in spinocerebellar ataxia type 3.Orphanet journal of rare diseases · 2026Article
- Gastrodin inhibits the formation of ataxin-3 aggregates by regulating the level of ERK1/2/P38 proteins.Orphanet journal of rare diseases · 2026Article
- Repeat-associated non-AUG translation as a common mechanism for the polyGln ataxias.Cell reports · 2026Article
- Extracellular vesicles-associated AAVs for the treatment of Machado-Joseph disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- The Status and Future Directions of Treatments for Polyglutamine Spinocerebellar Ataxia: A Bibliometric and Visual Analysis.Current neuropharmacology · 2026Review
- Brain atrophy staging in spinocerebellar ataxia type 3 for clinical prognosis and trial enrichment.EBioMedicine · 2026Article
- Treatment of primary adult-onset neurodegenerative cerebellar ataxias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Gene editing for Spinocerebellar ataxia type 3 taking advantage of the human ATXN3L paralog as replacement gene.Gene therapy · 2025Article
- Genome editing in spinocerebellar ataxia type 3 cells improves Golgi apparatus structure.Scientific reports · 2025Article
- Regional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3.Journal of neurology · 2024Article
- ASOs are an effective treatment for disease-associated oligodendrocyte signatures in premanifest and symptomatic SCA3 mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Spinocerebellar Ataxia Type 3 Pathophysiology-Implications for Translational Research and Clinical Studies.International journal of molecular sciences · 2024Review
- Review
- Blood levels of neurofilament light are associated with disease progression in a mouse model of spinocerebellar ataxia type 3.Disease models & mechanisms · 2023Article
- Regional sex differences in neurochemical profiles of healthy mice measured by magnetic resonance spectroscopy at 9.4 tesla.Frontiers in neuroscience · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveSpinocerebellar ataxia type 3 (SCA3) is the most common dominantly inherited ataxia, and biomarkers are needed to noninvasively monitor disease progression and treatment response. Anti-ATXN3 antisense oligonucleotide (ASO) treatment has been shown to mitigate neuropathology and rescue motor phenotypes in SCA3 mice. Here, we investigated whether repeated ASO administration reverses brainstem and cerebellar neurochemical abnormalities by magnetic resonance spectroscopy (MRS).
methodsSymptomatic SCA3 mice received intracerebroventricular treatment of ASO or vehicle and were compared to wild-type vehicle-treated littermates. To quantify neurochemical changes in treated mice, longitudinal 9.4T MRS of cerebellum and brainstem was performed. Acquired magnetic resonance (MR) group means were analyzed by 2-way analysis of variance mixed-effects sex-adjusted analysis with post hoc Sidak correlation for multiple comparisons. Pearson correlations were used to relate SCA3 pathology and behavior.
resultsMR spectra yielded 15 to 16 neurochemical concentrations in the cerebellum and brainstem. ASO treatment in SCA3 mice resulted in significant total choline rescue and partial reversals of taurine, glutamine, and total N-acetylaspartate across both regions. Some ASO-rescued neurochemicals correlated with reduction in diseased protein and nuclear ATXN3 accumulation. ASO-corrected motor activity correlated with total choline and total N-acetylaspartate levels early in disease.
interpretationSCA3 mouse cerebellar and brainstem neurochemical trends parallel those in patients with SCA3. Decreased total choline may reflect oligodendrocyte abnormalities, decreased total N-acetylaspartate highlights neuronal health disturbances, and high glutamine may indicate gliosis. ASO treatment fully or partially reversed select neurochemical abnormalities in SCA3 mice, indicating the potential for these measures to serve as noninvasive treatment biomarkers in future SCA3 gene silencing trials. ANN NEUROL 2023;94:658-671.
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.