Department of Pediatrics, Ohio State University, Columbus, Ohio.
Center for Gene Therapy Nationwide Children's Hospital, Columbus, Ohio.
Pediatr Pulmonol. 2019 Feb;54(2):179-185. doi: 10.1002/ppul.24203. Epub 2018 Dec 12.
Spinal Muscular Atrophy type 1 (SMA1) is a rare genetic neuromuscular disease where 75% of SMA1 patients die/require permanent-ventilation by 13.6 months. This study assessed the health outcomes of SMA1 infants treated with AVXS-101 gene replacement therapy.
Twelve genetically confirmed SMA1 infants with homozygous deletions of the SMN1 gene and two SMN2 gene copies received a one-time intravenous proposed therapeutic dose of AVXS-101 in an open label study conducted between December 2014 and 2017. Patients were followed for 2-years post-treatment for outcomes including (1) pulmonary interventions; (2) nutritional interventions; (3) swallow function; (4) hospitalization rates; and (5) motor function.
All 12 patients completed the study. Seven infants did not require noninvasive ventilation (NIV) by study completion. Eleven patients had stable or improved swallow function, demonstrated by the ability to feed orally; 11 patients were able to speak. The mean proportion of time hospitalized was 4.4%; the mean unadjusted annualized hospitalization rate was 2.1 (range = 0, 7.6), with a mean length of stay/hospitalization of 6.7 (range = 3, 12.1) days. Eleven patients achieved full head control and sitting unassisted and two patients were walking independently.
AVXS-101 treatment in SMA1 was associated with reduced pulmonary and nutritional support requirements, improved motor function, and decreased hospitalization rate over the follow-up period. This contrasts with the natural history of progressive respiratory failure and reduced survival. The reduced healthcare utilization could potentially alleviate patient and caregiver burden, suggesting an overall improved quality of life following gene replacement therapy.
ClinicalTrials.gov number, NCT02122952.
脊髓性肌萎缩症 1 型（SMA1）是一种罕见的遗传性神经肌肉疾病，75%的 SMA1 患者在 13.6 个月时死亡/需要永久性通气。本研究评估了接受 AVXS-101 基因替换治疗的 SMA1 婴儿的健康结果。
12 名经基因确认的 SMA1 婴儿，SMN1 基因纯合缺失，SMN2 基因拷贝数为 2，在 2014 年 12 月至 2017 年期间进行的一项开放标签研究中，接受了一次静脉内建议治疗剂量的 AVXS-101。在治疗后 2 年对患者进行了随访，以评估包括（1）肺部干预；（2）营养干预；（3）吞咽功能；（4）住院率；和（5）运动功能。
所有 12 名患者均完成了研究。7 名婴儿在研究结束时无需接受无创通气（NIV）。11 名患者吞咽功能稳定或改善，能够经口喂养；11 名患者能够说话。平均住院时间比例为 4.4%；未调整的年平均住院率为 2.1（范围为 0，7.6），平均住院时间/住院时间为 6.7（范围为 3，12.1）天。11 名患者实现了完全头部控制和无辅助坐立，2 名患者独立行走。
在 SMA1 中，AVXS-101 治疗与减少肺部和营养支持需求、改善运动功能以及在随访期间降低住院率相关。这与进行性呼吸衰竭和存活率降低的自然史形成对比。减少医疗保健的使用可能会减轻患者和护理人员的负担，这表明基因替换治疗后整体生活质量得到提高。
ClinicalTrials.gov 编号，NCT02122952。
