ArticleNeurobiology of disease2015
Assessing recovery from neurodegeneration in spinocerebellar ataxia 1: Comparison of in vivo magnetic resonance spectroscopy with motor testing, gene expression and histology.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- MRI end-points for clinical trials in ataxias: recommendations from the Ataxia Global Initiative MRI Biomarkers Working Group.Nature reviews. Neurology · 2026Review
- Antisense Oligonucleotide Silencing Reverses Abnormal Neurochemistry in Spinocerebellar Ataxia 3 Mice.Annals of neurology · 2023Article
- Neurochemical correlates of synapse density in a Huntington's disease mouse model.Journal of neurochemistry · 2023Article
- Cerebellar morphometric and spectroscopic biomarkers for Machado-Joseph Disease.Acta neuropathologica communications · 2022Article
- In Vivo Molecular Signatures of Cerebellar Pathology in Spinocerebellar Ataxia Type 3.Movement disorders : official journal of the Movement Disorder Society · 2020Article
- Collaborative Efforts for Spinocerebellar Ataxia Research in the United States: CRC-SCA and READISCA.Frontiers in neurology · 2020Review
- MR Imaging of SCA3/MJD.Frontiers in neuroscience · 2020Review
- Sensitivity of Volumetric Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy to Progression of Spinocerebellar Ataxia Type 1.Movement disorders clinical practice · 2019Article
- Antisense oligonucleotide-mediated ataxin-1 reduction prolongs survival in SCA1 mice and reveals disease-associated transcriptome profiles.JCI insight · 2018Article
- Spinocerebellar ataxias: prospects and challenges for therapy development.Nature reviews. Neurology · 2018Review
- Repeated Mesenchymal Stromal Cell Treatment Sustainably Alleviates Machado-Joseph Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Neurochemical abnormalities in premanifest and early spinocerebellar ataxias.Annals of neurology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Suppression of transgene expression in a conditional transgenic mouse model of spinocerebellar ataxia 1 (SCA1) reverses the Purkinje cell pathology and motor dysfunction that are hallmarks of SCA1. We previously showed that cerebellar neurochemical levels measured by magnetic resonance spectroscopy (MRS) correlate with progression of pathology and clinical status of patients and that abnormal neurochemical levels normalize upon suppression of transgene expression, indicating their potential as robust surrogate markers of treatment effects. Here we investigated the relative sensitivities of MRS, histology, transgene expression and motor behavioral testing to disease reversal in conditional SCA1 mice. Transgene expression was suppressed by doxycycline administration and treated and untreated mice were assessed by MRS at 9.4tesla before and after treatment and with an accelerating Rotarod, histology and quantitative polymerase chain reaction (qPCR) for ataxin-1 transgene expression following doxycycline treatment. The MRS-measured N-acetylaspartate-to-myo-inositol ratio (NAA/Ins) correlated significantly with the molecular layer (ML) thickness and transgene expression. NAA/Ins, ML thickness and transgene expression were highly significantly different between the treated vs. untreated groups (p<0.0001), while the Rotarod assessment showed a trend for treatment effect. MRS, qPCR and histology had high sensitivity/specificity to distinguish treated from untreated mice, all with areas under the curve (AUC)=0.97-0.98 in receiver operating characteristic (ROC) analyses, while Rotarod had significantly lower sensitivity and specificity (AUC=0.72). Therefore, MRS accurately reflects the extent of recovery from neurodegeneration with sensitivity similar to invasive measures, further validating its potential as a surrogate marker in pre-clinical and clinical treatment trials.
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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.