Bitetti Ilaria, Manna Maria Rosaria, Stella Roberto, Varone Antonio
Pediatric Neurology, Santobono-Pausilipon Children's Hospital, Naples, Italy.
Neurorehabilitation Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy.
Front Neurol. 2024 Feb 21;15:1326528. doi: 10.3389/fneur.2024.1326528. eCollection 2024.
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by mutations in the survival motor neuron 1 () gene. In clinical studies, gene replacement therapy with onasemnogene abeparvovec (formerly AVXS-101, Zolgensma, Novartis) was efficacious in improving motor functioning in children with SMA. However, its effects on cognitive and language skills are largely unknown.
This longitudinal observational study evaluated changes in motor and neurocognitive functioning over a 1-year period after administration of onasemnogene abeparvovec in 12 symptomatic SMA type 1 patients with two copies of aged 1.7-52.6 months at administration. Motor functioning was measured using the Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders (CHOP-INTEND) while neurocognitive assessment was measured using Griffiths III. Motor milestones and language ability were also assessed at each timepoint.
Statistically significant increases in median CHOP-INTEND scores from baseline were observed at 1, 3, 6, and 12 months after onasemnogene abeparvovec administration (all ≤ 0.005). Most (91.7%) patients were able to roll over or sit independently for >1 min at 12 months. Significant increases in the Griffiths III , and subscale scores were observed at 12-months, but not in the subscale. Speech and language abilities progressed in most patients. Overall, most patients showed some improvement in cognitive and communication performance after treatment with onasemnogene abeparvovec in addition to significant improvement in motor functioning and motor milestones. Evaluation of neurocognitive function should be considered when assessing the global functioning of patients with SMA.
脊髓性肌萎缩症（SMA）是一种由生存运动神经元1（SMN1）基因突变引起的神经退行性疾病。在临床研究中，onasemnogene abeparvovec（原称AVXS - 101，Zolgensma，诺华公司）基因替代疗法在改善SMA患儿的运动功能方面是有效的。然而，其对认知和语言技能的影响在很大程度上尚不清楚。
这项纵向观察性研究评估了12例有症状的1型SMA患者在接受onasemnogene abeparvovec治疗后1年内运动和神经认知功能的变化，这些患者在给药时年龄为1.7 - 52.6个月，携带两份SMN1基因拷贝。使用费城儿童医院婴儿神经肌肉疾病测试（CHOP - INTEND）测量运动功能，同时使用格里菲斯发育量表第三版（Griffiths III）进行神经认知评估。在每个时间点还评估了运动里程碑和语言能力。
在给予onasemnogene abeparvovec后的1、3、6和12个月，观察到CHOP - INTEND评分中位数较基线有统计学显著增加（所有P≤0.005）。大多数（91.7%）患者在12个月时能够翻身或独立坐立超过1分钟。在12个月时观察到格里菲斯III的个人 - 社会、精细动作和语言子量表得分显著增加，但在认知子量表中未观察到。大多数患者的言语和语言能力有所进步。总体而言，除了运动功能和运动里程碑有显著改善外，大多数患者在接受onasemnogene abeparvovec治疗后认知和沟通表现也有一定改善。在评估SMA患者的整体功能时，应考虑对神经认知功能进行评估。
