Rashin Mohseni1,2, Amir Ali Hamidieh3,4, Alireza Shoae-Hassani5, Masood Ghahvechi-Akbari6, Anahita Majma7, Mahmoud Mohammadi8, Mahin Nikougoftar9, Reza Shervin-Badv8, Jafar Ai2, Hadi Montazerlotfelahi10, Mahmoud Reza Ashrafi11,12. 1. Pediatric Cell and Gene Therapy Research Center (PCGTRC), Tehran University of Medical Sciences, Tehran, Iran. 2. Applied Cell Sciences and Tissue Engineering department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 3. Pediatric Cell and Gene Therapy Research Center (PCGTRC), Tehran University of Medical Sciences, Tehran, Iran. aahamidieh@tums.ac.ir. 4. Pediatric Hematology, Oncology and Stem Cell Transplantation Department, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. aahamidieh@tums.ac.ir. 5. Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran. 6. Department of Physical Medicine and Rehabilitation, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 7. Department of Pediatric Intensive Care Unit, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 8. Department of Pediatric Neurology, Growth and Development Research Center, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. 9. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran. 10. Department of Pediatric Neurology, Farhikhtegan Teaching Hospital, Islamic Azad, Tehran Medical Sciences, Tehran, Iran. 11. Pediatric Cell and Gene Therapy Research Center (PCGTRC), Tehran University of Medical Sciences, Tehran, Iran. ashrafim@tums.ac.ir. 12. Department of Pediatric Neurology, Growth and Development Research Center, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. ashrafim@tums.ac.ir.
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.
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.
Authors: Yang Xu; Ping Sun; Jian-Yu Wang; Zong-Ze Li; Rui-Lan Gao; Xue-Zhe Wang; William D Phillips; Simon X Liang Journal: Int J Mol Med Date: 2019-01-08 Impact factor: 4.101
Authors: Daniela N Urrutia; Pablo Caviedes; Rodrigo Mardones; José J Minguell; Ana Maria Vega-Letter; Claudio M Jofre Journal: PLoS One Date: 2019-03-11 Impact factor: 3.240