Mohseni Rashin, Hamidieh Amir Ali, Shoae-Hassani Alireza, Ghahvechi-Akbari Masood, Majma Anahita, Mohammadi Mahmoud, Nikougoftar Mahin, Shervin-Badv Reza, Ai Jafar, Montazerlotfelahi Hadi, Ashrafi Mahmoud Reza
Pediatric Cell and Gene Therapy Research Center (PCGTRC), Tehran University of Medical Sciences, Tehran, Iran.
Applied Cell Sciences and Tissue Engineering department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Neurol Sci. 2022 Jan;43(1):399-410. doi: 10.1007/s10072-021-05291-2. Epub 2021 May 25.
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).
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.
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).
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.
脊髓性肌萎缩症（SMA）是一种常染色体隐性遗传性脊髓α运动神经元神经退行性疾病，伴有进行性肌无力和肌张力减退，是婴儿死亡的最常见遗传原因。尽管SMA几乎没有有前景的治疗方法，但转化研究领域对此很活跃，基于干细胞的治疗临床试验或病例研究正在进行。采用不同治疗方法进行非治愈性治疗的联合应用可能会提高其有效性及患者的依从性。我们展示了一项针对1型SMA患者的1期临床试验，这些患者接受了侧群脂肪来源间充质干细胞（SPADMSCs）治疗。
干预组接受了3次鞘内注射递增剂量的SPADMSCs，并随访至24个月或生存时间。通过控制副作用进行安全性分析，并通过哈默史密斯婴儿神经学检查（HINE）、巴拉德评分和电诊断（EDX）评估进行疗效评估。这些评估在干预前和随访结束时进行。
治疗是安全且耐受性良好的，未出现任何与干细胞给药相关的不良事件。干预组中有一名患者在研究随访24个月后仍存活。他是一名62个月大的非独坐男孩，体重增加正常，每天需要约8小时无创通气（NIV）。临床评分、支持性通气需求和住院次数在干预组和对照组患者的反应中并非有意义的参数。干预组的所有5名患者胫神经运动幅度反应均有显著改善（0.56mV；p：0.029）。
本研究表明，SPADMSCs治疗在1型SMA中耐受性良好且安全，疗效有前景。可能与其他治疗策略相同，早期干预将提高其疗效，并为更多次注射争取时间。我们建议采用EDX评估来随访治疗效果。
