Abstract
The objective of this study is to synthesise the findings of clinical studies in order to derive evidence for use of the mesenchymal stem cell (MSC) therapy in the treatment of neurodegenerative cerebellar ataxias. In order to find relevant studies for the systematic review, we searched through Medline (1985 to July 2020), PubMed and Clinical trial register. We included both single-arm and comparative studies in which MSCs were given as intervention in neurodegenerative ataxia patients at any time after the diagnosis. We used Joanna Briggs Institute (JBI) quality scale to evaluate the methodological qualities of the included studies. Our literature search obtained 81 publications. Three articles comprising a total of 47 patients were included in the meta-analysis. None of them were randomised controlled trials (RCTs). Pooled analysis noted that there was a decrease in the Berg Balance Scale (BBS)/Scale for the Assessment and Rating of Ataxia (SARA) score from pre to post assessment; however, the difference was statistically not significant (standardised mean difference (SMD) − 0.20; 95% CI − 0.78 to 0.38). No significant side effects were reported in any of the studies. We did not observe any statistically significant difference in the pooled mean difference in the International Cooperative Ataxia Rating Scale (ICARS) score between pre and post assessment in patients with ataxia after receiving the stem cells (SMD 0.36, 95% CI − 0.08 to 0.81). Our systematic review and meta-analysis concluded that MSC cell therapy appeared safe but provided insufficient evidence to support the use of MSCs to treat patients with neurodegenerative cerebellar ataxia at present. No l RCTs was available in the literature to test efficacy; therefore, well-designed RCTs are needed to ascertain the effectiveness of MSCs in patients with neurodegenerative cerebellar ataxias.
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Abbreviations
- BBS:
-
Berg Balance Scale
- ICARS:
-
International Cooperative Ataxia Rating Scale
- SARA:
-
Scale for the Assessment and Rating of Ataxia
- SMD:
-
Standardised mean difference
References
Ashizawa T, Xia G. Ataxia. Contin Lifelong Learn Neurol. 2016;22:1208–26.
Yabe I. Sasaki H [Advances in neurological therapeutics for Friedreich ataxia and Machado-Joseph disease]. Brain Nerve Shinkei Kenkyu No Shinpo. 2017;69:913–24.
Kearney M, Orrell RW, Fahey M, Brassington R, Pandolfo M. Pharmacological treatments for Friedreich ataxia. Cochrane Database Syst Rev [Internet]. 2016 [cited 2019 Sep 20]; Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007791.pub4/full?highlightAbstract=ataxia%7Cwithdrawn%7Cataxi
Vogel AP, Folker J, Poole ML. Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes. Cochrane Database Syst Rev [Internet]. 2014 [cited 2019 Sep 20]; Available from: https://www.cochranelibrary.com/cdsr/doi/https://doi.org/10.1002/14651858.CD008953.pub2/full?highlightAbstract=withdrawn%7Cataxi%7Cataxia%7Cspinocerebellar
Koller WC. Pharmacologic trials in the treatment of cerebellar tremor. Neurology [Internet]. 33 Suppl 2 [cited 2020 Jan 6]; Available from: https://www.cochranelibrary.com/central/doi/https://doi.org/10.1002/central/CN-00446139/full
Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med. 2004;8:301–16.
Duncan T, Valenzuela M. Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res Ther [Internet]. 2017 [cited 2020 Jan 6];8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427593/
Zeng L, Chan LL, Lim EC, Tan EK. Stem cell replacement therapies in Parkinson’s disease. 2019;48:3
Aliaghaei A, Boroujeni ME, Ahmadi H, Bayat A-H, Tavirani MR, Abdollahifar MA, et al. Dental pulp stem cell transplantation ameliorates motor function and prevents cerebellar atrophy in rat model of cerebellar ataxia. Cell Tissue Res. 2019;376:179–87.
Chintawar S, Hourez R, Ravella A, Gall D, Orduz D, Rai M, et al. Grafting neural precursor cells promotes functional recovery in an SCA1 mouse model. J Neurosci. 2009;29:13126–35.
Lukovic D, Moreno-Manzano V, Rodriguez-Jimenez FJ, Vilches A, Sykova E, Jendelova P, et al. hiPSC disease modeling of rare hereditary cerebellar ataxias: opportunities and future challenges. Neuroscientist. 2017;23:554–66.
Jones J, Jaramillo-Merchán J, Bueno C, Pastor D, Viso-León M, Martínez S. Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia. Neurobiol Dis. 2010;40:415–23.
Chang Y-K, Chen M-H, Chiang Y-H, Chen Y-F, Ma W-H, Tseng C-Y, et al. Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells. J Biomed Sci. 2011;18:54.
Arien-Zakay H, Lecht S, Bercu MM, Tabakman R, Kohen R, Galski H, et al. Neuroprotection by cord blood neural progenitors involves antioxidants, neurotrophic and angiogenic factors. Exp Neurol. 2009;216:83–94.
Dongmei H, Jing L, Mei X, Ling Z, Hongmin Y, Zhidong W, et al. Clinical analysis of the treatment of spinocerebellar ataxia and multiple system atrophy-cerebellar type with umbilical cord mesenchymal stromal cells. Cytotherapy. 2011;13:913–7.
Jin J-L, Liu Z, Lu Z-J, Guan D-N, Wang C, Chen Z-B, et al. Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia [Internet]. 2013 [cited 2020 Jan 6]. Available from: https://www.ingentaconnect.com/content/ben/cnr/2013/00000010/00000001/art00003
Tsai Y-A, Liu R-S, Lirng J-F, Yang B-H, Chang C-H, Wang Y-C, et al. Treatment of spinocerebellar ataxia with mesenchymal stem cells: a phase I/IIa clinical study. Cell Transplant. 2017;26:503–12.
Yang W-Z, Zhang Y, Wu F, Zhang M, Cho S, Li C-Z, et al. Human umbilical cord blood-derived mononuclear cell transplantation: case series of 30 subjects with hereditary ataxia. J Transl Med. 2011;9:65.
Ma L-L, Wang Y-Y, Yang Z-H, Huang D, Weng H, Zeng X-T. Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better? Mil Med Res. 2020;7:7.
Appelt PA, Comella K, de Souza LAPS, Luvizutto GJ. Effect of stem cell treatment on functional recovery of spinocerebellar ataxia: systematic review and meta-analysis. Cerebellum Ataxias. 2021;8:8.
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Bhartiya, M., Kumar, A., Singh, R.K. et al. Mesenchymal Stem Cell Therapy in the Treatment of Neurodegenerative Cerebellar Ataxias: a Systematic Review and Meta-analysis. Cerebellum 22, 363–369 (2023). https://doi.org/10.1007/s12311-022-01403-6
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DOI: https://doi.org/10.1007/s12311-022-01403-6