Measuring Outcomes in Adults with Spinal Muscular Atrophy - Challenges and Future Directions - Meeting Report
Measuring Outcomes in Adults with Spinal Muscular Atrophy - Challenges and Future Directions - Meeting Report
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DOI：
10.3233/jnd-200534
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Hagenacker, T.
中科院分区：
文献类型：
--
作者：
Sansone, V. A.;Walter, M. C.;Hagenacker, T.
脊髓性肌萎缩症(SMA)是一种进行性常染色体隐性运动神经元病，由存活运动神经元1基因(SMN1)缺失引起，每6,000-10,000名活产儿中就有1例发病。治疗发展的一个主要焦点是通过增加SMN2转录本中外显子7的包含来增加全长SMN蛋白，增强SMN2基因的表达，稳定SMN蛋白或取代SMN1基因。2017年6月，FDA和EMA批准反义寡核苷酸Nusinesen作为治疗所有SMA亚型的第一种药物，而不受年龄限制。虽然在疾病的早期阶段和15岁以下的患者中观察到了显著的治疗效果，但在成年SMA患者的临床试验中只有有限的数据。来自神经肌肉临床中心的第一个真实世界数据表明，在成人SMA患者中，Nusinesen也具有良好的安全性：在几个病例中，运动功能得到了相应的改善，这可能会增强日常生活活动的自主性，改善生活质量。使用经过验证的仪器对运动状态进行系统的跟踪对于充分监测治疗效果至关重要，但大多数广泛使用的量表和评分仅针对儿科人群进行了评估。国际神经肌肉专家于2019年5月在德国法兰克福/美因河畔举行会议，讨论成人SMA诊断途径和患者管理的相关方面。对这些患者群体的建议和挑战进行了讨论。
Spinal muscular atrophy (SMA) is a progressive autosomal recessive motor neuron disease which affects 1 in 6,000-10,000 live births, caused by loss of the survival motor neuron 1 gene (SMN1). A major focus of therapeutic developments has been on increasing the full-length SMN protein by increasing the inclusion of exon 7 in SMN2 transcripts, enhancing SMN2 gene expression, stabilizing the SMN protein or replacing the SMN1 gene.In June 2017, FDA and EMA have approved the antisense oligonucleotide Nusinersen as the first treatment for all SMA subtypes without age restriction. While prominent treatment effects have been observed in the earlier stages of the disease and in patients up to 15 years of age, there is only limited data from clinical trials in adult SMA patients. First real-world data from neuromuscular clinical centers suggest a therapeutic benefit of nusinersen with a favourable safety profile also in adult SMA patients: in several cases, relevant improvements of motor function is achieved, which might lead to enhanced autonomy in daily life activities and improved quality of life. Systematic follow-up of the motor status with validated instruments is crucial for an adequate monitoring of the therapeutic effects but most of the widely used scales and scores have been developed and evaluated for the pediatric population only. International neuromuscular experts have met in Frankfurt/Main, Germany in May 2019 to discuss relevant aspects of the diagnostic pathway and patient management in adult SMA. The recommendations and challenges in this patient population are discussed.