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. 2018;5(2):135-143.
doi: 10.3233/JND-180315.

Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany

Astrid Pechmann  1 , Thorsten Langer  1 , David Schorling  1 , Sabine Stein  1 , Sibylle Vogt  1 , Ulrike Schara  2 , Heike Kölbel  2 , Oliver Schwartz  3 , Andreas Hahn  4 , Kerstin Giese  4 , Jessika Johannsen  5 , Jonas Denecke  5 , Claudia Weiß  6 , Manuela Theophil  7 , Janbernd Kirschner  1
Affiliations

Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany

Astrid Pechmann et al. J Neuromuscul Dis. 2018.

Abstract

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle weakness and muscle atrophy. Nusinersen acts as a splicing modifier and has recently been approved for intrathecal treatment of SMA.

Objective: Prior to approval, nusinersen was provided to patients with SMA type 1 in Germany within an Expanded Access Program (EAP). In contrast to previous clinical trials, children of different age groups and different stages of the disease were treated with nusinersen.

Methods: We conducted a prospective, longitudinal data collection of patients treated with nusinersen within the EAP in seven neuromuscular centers in Germany. Standardized assessments including CHOP-INTEND and HINE-2 motor milestones were performed at baseline and 60 and 180 days after start of treatment.

Results: Data from 61 SMA type 1 patients (mean age 21.08 months, range 1-93) were available for analysis. After six months of treatment, 47 children (77.0%) improved by ≥4 points in CHOP INTEND score. Mean change in CHOP INTEND score was 9.0±8.0 points. Nineteen patients (31.1%) improved by ≥2 points in HINE-2 motor milestones. Regression analysis revealed age at onset of treatment as major determinant of change in CHOP INTEND from baseline.

Conclusion: When analyzing a broad spectrum of SMA type 1 patients, many children showed an improvement of motor function after six months of treatment with nusinersen, which is generally not expected within the natural course of the disease. Long-term observation and follow-up of patients with later onset types of SMA are crucial to understand the clinical impact of treatment with nusinersen.

Keywords: SMArtCARE; Spinal muscular atrophy; motor function; motor milestones; nusinersen.

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Figures

Fig.1
Fig.1
Longitudinal CHOP INTEND score according to age at onset of treatment. Colors are for visualization only.
Fig.2
Fig.2
Longitudinal HINE-2 score according to age at onset of treatment. Colors are for visualization only.
Fig.3
Fig.3
Data at baseline and after six months of treatment regarding ventilator support (a) and nutrition (b).
See this image and copyright information in PMC

References

    1. Sanctis R de, Coratti G, Pasternak A, Montes J, Pane M, Mazzone ES, et al. Developmental milestones in type I spinal muscular atrophy. Neuromuscul Disord. 2016;26(11):754–9. - PMC - PubMed
    1. Pechmann A, Kirschner J. Diagnosis and new treatment avenues in spinal muscular atrophy. Neuropediatrics. 2017;48(4):273–81. - PubMed
    1. Passini MA, Bu J, Richards AM, Kinnecom C, Sardi SP, Stanek LM, et al. Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy. Sci Transl Med. 2011;3(72):72ra18. - PMC - PubMed
    1. Singh NK, Singh NN, Androphy EJ, Singh RN. Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron. Mol Cell Biol. 2006;26(4):1333–46. - PMC - PubMed
    1. Lorson CL, Androphy EJ. An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN. Hum Mol Genet. 2000;9(2):259–65. - PubMed