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Background <p>Hereditary cerebellar ataxias (HCA) encompass a spectrum of pathological conditions affecting the cerebellum. Currently, there is growing interest in the potential role of mesenchymal stem cells (MSCs) as an investigational therapeutic approach for this condition. Hence, the objective of this single-center, open-label, phase I/IIa clinical trial was to assess the safety and exploratory clinical and biomarker changes following a single intrathecal injection of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in HCA.</p> Methods <p>Ten confirmed patients with HCA entered the study and underwent a single dose of (1 × 10<sup>6</sup> cells/kg BW) intrathecal transplantation of BM-MSCs at passage 3. During the follow-up, patients were evaluated four times (one month before the intervention (-1), months 1, 3, and 6). Assessments included safety evaluation, Scale for the Assessment and Rating of Ataxia (SARA), GAD 65-antibody, and specific cytokines in the patient’s serum and cerebrospinal fluid (CSF) samples.</p> Results <p>No severe adverse effects were observed following the cell transplantation procedure. A decreasing trend in SARA score was observed, with a statistically significant difference at month 6 compared with baseline. Except for one patient, GAD-65 antibody levels remained within the normal range in all patients. In one patient with markedly elevated baseline GAD-65 titers, serum and CSF GAD-65 levels decreased from 814 IU/mL and 781 IU/mL, respectively, to values within the normal range after 3 months. Significant changes were observed in selected inflammatory biomarkers, including decreased serum IL-6 at month 3, decreased CSF TNF-alpha at months 1 and 3, and increased serum IL-10 during follow-up. CSF IL-6 did not show a significant decrease.</p> Conclusion <p>The findings support the short-term safety and tolerability of a single intrathecal dose of autologous BM-MSCs in this small HCA cohort. The study provides preliminary signals of possible clinical and biomarker changes; however, efficacy cannot be established due to the uncontrolled design, small sample size, disease heterogeneity, and short follow-up. Larger randomized controlled trials are required to validate these exploratory findings.</p> <p><i>Trial registration:</i> This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N3).</p>

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Safety and preliminary efficacy of autologous bone marrow-derived mesenchymal stem cell transplantation in hereditary cerebellar ataxia: phase I/IIa clinical trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月10日

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  • Abbas Shapouri Moghaddam,
  • Jalil Tavakol-Afshari,
  • Najmeh Kaffash Farkhad,
  • Majid Mojarrad,
  • Maryam Eslami,
  • Shahram Savad,
  • Mohammad Ali Khodadoust,
  • Ala Orafaie,
  • Mohammadreza Sobhani,
  • Akram Farmanbar,
  • Mohammad Dashtkoohi,
  • Hamid Khodayari,
  • Delaram Hassani,
  • Shahrzad Najafi,
  • Parizad Najafi,
  • Jürgen Hescheler,
  • Karim Nayernia,
  • Amirreza Boroumand

摘要

Background

Hereditary cerebellar ataxias (HCA) encompass a spectrum of pathological conditions affecting the cerebellum. Currently, there is growing interest in the potential role of mesenchymal stem cells (MSCs) as an investigational therapeutic approach for this condition. Hence, the objective of this single-center, open-label, phase I/IIa clinical trial was to assess the safety and exploratory clinical and biomarker changes following a single intrathecal injection of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in HCA.

Methods

Ten confirmed patients with HCA entered the study and underwent a single dose of (1 × 106 cells/kg BW) intrathecal transplantation of BM-MSCs at passage 3. During the follow-up, patients were evaluated four times (one month before the intervention (-1), months 1, 3, and 6). Assessments included safety evaluation, Scale for the Assessment and Rating of Ataxia (SARA), GAD 65-antibody, and specific cytokines in the patient’s serum and cerebrospinal fluid (CSF) samples.

Results

No severe adverse effects were observed following the cell transplantation procedure. A decreasing trend in SARA score was observed, with a statistically significant difference at month 6 compared with baseline. Except for one patient, GAD-65 antibody levels remained within the normal range in all patients. In one patient with markedly elevated baseline GAD-65 titers, serum and CSF GAD-65 levels decreased from 814 IU/mL and 781 IU/mL, respectively, to values within the normal range after 3 months. Significant changes were observed in selected inflammatory biomarkers, including decreased serum IL-6 at month 3, decreased CSF TNF-alpha at months 1 and 3, and increased serum IL-10 during follow-up. CSF IL-6 did not show a significant decrease.

Conclusion

The findings support the short-term safety and tolerability of a single intrathecal dose of autologous BM-MSCs in this small HCA cohort. The study provides preliminary signals of possible clinical and biomarker changes; however, efficacy cannot be established due to the uncontrolled design, small sample size, disease heterogeneity, and short follow-up. Larger randomized controlled trials are required to validate these exploratory findings.

Trial registration: This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N3).