Fatigue in adults with spinal muscular atrophy under treatment with nusinersen

K Kizina,C Ose,S Bolz,C Kleinschnitz,Tim Hagenacker,O Von Velsen,M Schlag,B Stolte,A Totzeck

doi:10.1038/s41598-020-68051-w

Abstract

5q-Associated spinal muscular atrophy is a hereditary neuromuscular disease leading to progressive muscle weakness in which fatigue occurs and affects quality of life. Treatment with the antisense oligonucleotide nusinersen has been shown to improve motor function. Fatigue can be measured within the Fatigue Severity Scale (FSS). FSS is a self-reported questionnaire consisting of nine items to quantify fatigue severity within the last week. Higher values indicating a higher severity. Using the FSS, fatigue was measured in 28 adult patients, subdivided into ambulatory and non-ambulatory, suffering from a genetically confirmed 5q-SMA under treatment with nusinersen in accordance with the label. Correlations were performed among FSS and motor scales, 6-minute walk test (6MWT) and Hammersmiths Functional Motor Scale Expanded (HFMSE). Evaluation was performed prior to treatment initiation and after 6 and 10 months. The mean FSS score for all 28 patients at baseline was 4.61 ± 1.44. After 6 months mean FSS score significantly reduced to 3.92 ± 1.35. After 10 months mean FSS score had not differed from baseline, 3.84 ± 1.25. A moderate negative correlation of the difference of FSS and 6MWT after 6 months compared to baseline conditions was measured. Nusinersen reduces fatigue as measured by the FSS in adult patients with 5q-SMA transiently after initiation of treatment. There was no reduction of FSS 10 months after the beginning of treatment when compared to baseline.

Highlights

5q-Associated spinal muscular atrophy is a hereditary neuromuscular disease leading to progressive muscle weakness in which fatigue occurs and affects quality of life
5q-Spinal muscular atrophy (5q-SMA) is an autosomal-recessive neuromuscular disease with an incidence of 1:10,000, and is caused by a homozygous mutation or deletion of survival of the motor neuron 1 gene (SMN1) located on chromosome 5q, which impedes the sufficient production of SMN proteins[1,2]
The 18 male and 10 female patients treated had a mean age of 37 years

Summary

Introduction

5q-Associated spinal muscular atrophy is a hereditary neuromuscular disease leading to progressive muscle weakness in which fatigue occurs and affects quality of life. Nusinersen reduces fatigue as measured by the FSS in adult patients with 5q-SMA transiently after initiation of treatment. Abbreviations 6MWT 6-Minute walk test ASO Antisense oligonucleotide DMD Duchenne muscular dystrophy EMA European Medicines Agency FSS Fatigue Severity Scale HFMSE Hammersmith Functional Motor Scale Expanded IRC Item-rest correlation MS Multiple sclerosis RULM Revised Upper Limb Module SLE Systemic lupus erythematosus SMA Spinal muscular atrophy SMN Survival of motoneuron. 5q-Spinal muscular atrophy (5q-SMA) is an autosomal-recessive neuromuscular disease with an incidence of 1:10,000, and is caused by a homozygous mutation or deletion of survival of the motor neuron 1 gene (SMN1) located on chromosome 5q, which impedes the sufficient production of SMN proteins[1,2] It leads to progressive muscle atrophy and weakness due to the degeneration of the anterior horn cells[3]. The FSS has been used frequently to objectify fatigue in neuro-degenerative diseases[13,14,15] and in neuromuscular diseases, such as Duchenne muscular dystrophy or 5q-SMA16

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Conclusion