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KMID : 0390320210310010009
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Chungbuk Medical Journal
2021 Volume.31 No. 1 p.9 ~ p.18
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Antisense Oligonucleotide Therapy in Children with Spinal Muscular Atrophy
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Yun Hee-Jeong
Kim Won-Seop
Kim Jon-Soo
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Abstract
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Purpose: The antisense oligonucleotide nusinersen recently became the first approved drug against spinal muscular atrophy (SMA). Nusinersen is administered directly into the cerebrospinal fluid and alters SMN2 pre-mRNA splicing of exon 7, thus increasing the expression of functional SMN protein. Clinical trial data on the use of nusinersen are still lacking. We describe our experience of the use of intrathecal nusinersen in children with SMA at our center.
Methods: Nusinersen(12mg) was administered intrathecally according to a standard protocol to children with SMA hospitalized at our center. All procedures required moderate to deep sedation using intravenous midazolam or ketamine to minimize movements. Vital signs, and the need for oxygen and analgesia during the procedure were monitored. Functional assessment, including Hammersmith Functional Motor Scale (HFMSE) motor milestones, was performed at baseline and after 3rd, 4th, 5th, and 6th administrations.
Results: Five female patient (aged 38.7 to 84.8 months) with SMA type 2 (all 3 copies of SMN2 gene) successfully completed the treatment (6th administration of nusinersen). All patients had mild scoliosis; however, they did not need ventilatory support. All procedures were performed safely, without any complications. Two patients had fever shortly after the procedure. After the 6th administration, all children showed improvement of at least ≥ 2 points in the HFMSE score (mean 4.4 points). Three children (60.0%) showed functional improvements from the 3rd dose. In particular, parents reported that the children's overall strength and endurance had improved. In addition, their ability to cough improved.
Conclusion: Intrathecal nusinersen was administered safely and caused an improvement in motor function within a short period. Long-term observation and follow-up of patients are crucial to understand the clinical impact of treatment with nusinersen.
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KEYWORD
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Spinal muscular atrophy, Nusinersen, Antisense oligonucleotide therapy
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