Treatment of cerebellar ataxia with mesenchymal stem cells: a phase I/II trial

  • B. Soong
    2Prof. & Chairman, Dept. of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan

    4Prof. & Chairman, Dept. of Neurology, National Yang Ming University, Taipei, Taiwan
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  • O. Lee
    1Director, Stem Cell Research Center, National Yang Ming University, Taipei, Taiwan

    3Deputy Dean, Office of International Affairs, National Yang Ming University, Taipei, Taiwan

    5Prof., Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan
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      Spinocerebellar ataxias (SCA), are determined rare diseases by the Office of Rare Diseases Research at the National Institutes of Health. SCA causes progressive difficulty with coordination and gait which interferes in performing normal daily functions. SCA patients die from respiratory failure, aspiration pneumonia, or severe infection within 20 years of onset. There are no approved therapeutics for treating SCA (spinocerebellar ataxia). PolyQ SCAs are caused by an extensive CAG sequence repeat which encodes for expanded polyQ residues within the mutated protein. All polyQ SCA patients clinically present limb and gait ataxia because the same ataxia interactome is shared among sub-groups. Extensive polyQ in cells, including Purkinje neurons, leads to cell dysfunction and triggers cell apoptosis. Loss of Purkinje cells leads to the symptoms and disease outcomes of SCA. Our pre-clinical research has achieved pre-clinical evidence suggesting adipose tissue-derived mesenchymal stem cell (ADMSC) transplantation ameliorates motor function deterioration of SCA in SCA2 transgenic mice by rescuing cerebellar Purkinje cells (Journal of Biomedical Science 2011, 18:54; Chang, et al). The infusion of ADMSC-derived Stemchymal MSCs into SCA patients may be safe and may demonstrate evidence of ameliorating motor function deterioration by arresting continued loss of Purkinje cells to premature apoptosis caused by oxidative stress from excessive PolyQ expression. Our trial design includes a single 7 x107 Stemchymal cells infusion into seven patients with 12 months follow up. Primary outcome measures for safety include vital signs, clinical lab tests and adverse events. Secondary outcome measures for early evidence of efficacy include changes in the scale for the assessment and rating of ataxia (SARA) score, changes in sensory organization test (SOT) score, changes in adaptation test (ADT) scores and changes in electronystagmogram (ENG). At 10 months, Phase I / II safety and early efficacy data supports the feasibility of using allogeneic Stemchymal(TM) Cell Therapy in the treatment of SCA patients. Longer term follow-up and larger, well-controlled clinical trials will be required to get to reach a definitive conclusion for Stemchymal treatment of SCA.
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