ArticleMovement disorders : official journal of the Movement Disorder Society2021
A Chlorzoxazone-Baclofen Combination Improves Cerebellar Impairment in Spinocerebellar Ataxia Type 1.
Article in Movement disorders : official journal of the Movement Disorder Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Resilience to Endoplasmic Reticulum Stress Mitigates Membrane Hyperexcitability Underlying Late Disease Onset in a Murine Model of SCA6.Annals of neurology · 2026Article
- Treatment of primary adult-onset neurodegenerative cerebellar ataxias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- TMEM206 gene knockout improves balance performance in SCA1 transgenic mice.IBRO neuroscience reports · 2025Article
- SMPR: a structure-enhanced multimodal drug‒disease prediction model for drug repositioning and cold start.Journal of cheminformatics · 2025Article
- Fingolimod Prevents Neuroinflammation but Has a Limited Effect on the Development of Ataxia in a Mouse Model for SCA1.International journal of molecular sciences · 2025Article
- Increased intrinsic membrane excitability is associated with olivary hypertrophy in spinocerebellar ataxia type 1.Human molecular genetics · 2024Article
- Potential Benefit of Channel Activators in Loss-of-Function Primary Potassium Channelopathies Causing Heredoataxia.Cerebellum (London, England) · 2024Review
- Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1.Neuron · 2024Article
- Spinocerebellar ataxias: from pathogenesis to recent therapeutic advances.Frontiers in neuroscience · 2024Review
- Increased intrinsic membrane excitability is associated with hypertrophic olivary degeneration in spinocerebellar ataxia type 1.bioRxiv : the preprint server for biology · 2023Article
- Physiological Recordings of the Cerebellum in Movement Disorders.Cerebellum (London, England) · 2023Review
- Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.Life (Basel, Switzerland) · 2023Review
- Therapeutic Strategies for Spinocerebellar Ataxia Type 1.Biomolecules · 2023Review
- Mechanistic Insights and Potential Therapeutic Approaches in PolyQ Diseases via Autophagy.Biomedicines · 2023Review
- Electrophysiological Studies Support Utility of Positive Modulators of SK Channels for the Treatment of Spinocerebellar Ataxia Type 2.Cerebellum (London, England) · 2022Review
- Discovery of Novel Activators of Large-Conductance Calcium-Activated Potassium Channels for the Treatment of Cerebellar Ataxia.Molecular pharmacology · 2022Article
- Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications.Cerebellum (London, England) · 2022Article
- Current and emerging treatment modalities for spinocerebellar ataxias.Expert review of neurotherapeutics · 2022Review
- Vulnerability of Human Cerebellar Neurons to Degeneration in Ataxia-Causing Channelopathies.Frontiers in systems neuroscience · 2022Review
- Single nuclei RNA sequencing investigation of the Purkinje cell and glial changes in the cerebellum of transgenic Spinocerebellar ataxia type 1 mice.Frontiers in cellular neuroscience · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundA combination of central muscle relaxants, chlorzoxazone and baclofen (chlorzoxazone-baclofen), has been proposed for treatment of cerebellar symptoms in human spinocerebellar ataxia. However, central muscle relaxants can worsen balance. The optimal dose for target engagement without toxicity remains unknown. Using the genetically precise Atxn1
methodsWe use patch clamp electrophysiology in acute cerebellar slices and immunostaining to identify the specific ion channels targeted by chlorzoxazone-baclofen. Behavioral assays for coordination and grip strength are used to determine specificity of chlorzoxazone-baclofen for improving cerebellar dysfunction without off-target effects in Atxn1
resultsWe identify irregular Purkinje neuron firing in association with reduced expression of ion channels Kcnma1 and Cacna1g in Atxn1
conclusionWe identify a tight relationship between baclofen-chlorzoxazone concentrations needed to engage target and levels above which cerebellar function will be compromised. We propose to use this information for a novel clinical trial design, using sequential dose escalation within each subject, to identify dose levels that are likely to improve ataxia symptoms while minimizing toxicity. © 2020 International Parkinson and Movement Disorder Society.
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