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An open-label phase 1 clinical trial of the allogeneic side population adipose-derived mesenchymal stem cells in SMA type 1 patients

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Abstract

Introduction

Spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disorder of alpha motor neurons of spinal cord associated with progressive muscle weakness and hypotonia, is the most common genetic cause of infant mortality. Although there is few promising treatment for SMA, but the field of translational research is active in it, and stem cell-based therapy clinical trials or case studies are ongoing. Combination of different therapeutic approaches for noncurative treatments may increase their effectiveness and compliance of patients. We present a phase 1 clinical trial in patients with SMA1 who received side population adipose-derived mesenchymal stem cells (SPADMSCs).

Methods

The intervention group received three intrathecal administrations of escalating doses of SPADMSCs and followed until 24 months or the survival time. The safety analysis was assessed by controlling the side effects and efficacy evaluations performed by the Hammersmith Infant Neurological Examination (HINE), Ballard score, and electrodiagnostic (EDX) evaluation. These evaluations were performed before intervention and at the end of the follow-up.

Results

The treatment was safe and well tolerated, without any adverse event related to the stem cell administration. One of the patients in the intervention group was alive after 24 months of study follow-up. He is a non-sitter 62-month-old boy with appropriate weight gain and need for noninvasive ventilation (NIV) for about 8 h per day. Clinical scores, need for supportive ventilation, and number of hospitalizations were not meaningful parameters in the response of patients in the intervention and control groups. All five patients in the intervention group showed significant improvement in the motor amplitude response of the tibial nerve (0.56mV; p: 0.029).

Conclusion

This study showed that SPADMSCs therapy is tolerable and safe with promising efficacy in SMA I. Probably same as other treatment strategies, early intervention will increase its efficacy and prepare time for more injections. We suggest EDX evaluation for the follow-up of treatment efficacy.

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Data availability

All of the data and material is available in the Pediatrics Cell Therapy Research Center of the Tehran University of Medical Sciences. The data will be available on the ClinicalTrials.gov with the identifier no.: NCT02855112.

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Acknowledgements

The authors thank the anonymous referees for their time.

Funding

This project was completely supported by the Tehran University of Medical Sciences by the Grant No: 94-01-87-28524 for the clinical trial program in SMA1 (Werdnig Hoffman) patients.

Author information

Authors and Affiliations

  1. Pediatric Cell and Gene Therapy Research Center (PCGTRC), Tehran University of Medical Sciences, Tehran, Iran

    Rashin Mohseni, Amir Ali Hamidieh & Mahmoud Reza Ashrafi

  2. Applied Cell Sciences and Tissue Engineering department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Rashin Mohseni & Jafar Ai

  3. Pediatric Hematology, Oncology and Stem Cell Transplantation Department, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Amir Ali Hamidieh

  4. Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran

    Alireza Shoae-Hassani

  5. Department of Physical Medicine and Rehabilitation, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Masood Ghahvechi-Akbari

  6. Department of Pediatric Intensive Care Unit, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Anahita Majma

  7. Department of Pediatric Neurology, Growth and Development Research Center, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Mahmoud Mohammadi, Reza Shervin-Badv & Mahmoud Reza Ashrafi

  8. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran

    Mahin Nikougoftar

  9. Department of Pediatric Neurology, Farhikhtegan Teaching Hospital, Islamic Azad, Tehran Medical Sciences, Tehran, Iran

    Hadi Montazerlotfelahi

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  1. Rashin Mohseni
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  11. Mahmoud Reza Ashrafi
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Contributions

RM carried out cell harvest, culture, and characterization, AH participated in the design and conduction of the study, AS participated in quality control test and final approval of the stem cell products, MG carried out EMG and NCV, AM selected the patients according to the criteria, MM visited all patients, JA wrote the manuscript draft, MN carried out immunophenotyping, RS participated in visiting patients, HM participated in stem cell administration to patients, and MRA participated in its design, patient selection, and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Amir Ali Hamidieh or Mahmoud Reza Ashrafi.

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Competing interest

The authors declare no competing interests.

Ethical approval

This study approved by the ethical committee of the Tehran University of Medical Sciences and the Iranian Ministry of Health and Medical Education (MOHME) Ethics board, Tehran, Iran.

Informed consent

The informed consent forms were filled by the legal guardian (parents) of the all participants in our intervention. All donors entering the program agreed to and signed an institutional review board-approved statement of informed consent.

Consent for publication

All the consent forms are signed by the parents of the patients or their legal representatives. A copy of the signed consent forms is available in the supplementary file section.

Statement of human and animal rights

All of the experimental procedures involving animals were conducted in accordance with the institutional animal care guidelines of Tehran University of Medical Sciences and approved by the administration committee of Experimental Animals, Tehran, Iran.

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Mohseni, R., Hamidieh, A.A., Shoae-Hassani, A. et al. An open-label phase 1 clinical trial of the allogeneic side population adipose-derived mesenchymal stem cells in SMA type 1 patients. Neurol Sci 43, 399–410 (2022). https://doi.org/10.1007/s10072-021-05291-2

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  • DOI: https://doi.org/10.1007/s10072-021-05291-2

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