Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study

Hagenacker, Tim; Wurster, Claudia D.; Günther, René; Schreiber‐Katz, Olivia; Osmanovic, Alma; Petri, Susanne; Weiler, Markus; Ziegler, Andreas; Kuttler, Josua; Koch, Jan Christoph; Schneider, Ilka; Wunderlich, Gilbert; Schloss, Natalie; Lehmann, Helmar C.; Cordts, Isabell; Deschauer, Marcus; Lingor, Paul; Kamm, Christoph; Stolte, Benjamin; Pietruck, Lena; Totzeck, Andreas; Kizina, Kathrin; Mönninghoff, Christoph; Velsen, Otgonzul von; Ose, Claudia; Reichmann, Heinz; Forsting, Michael; Pechmann, Astrid; Kirschner, Janbernd; Ludolph, Albert C.; Hermann, Andreas; Kleinschnitz, Christoph

doi:10.1016/s1474-4422(20)30037-5

Cited by 249 publications

(336 citation statements)

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“…A further analysis prompted by the need to have reference data for the increasingly available 12-month data in treated pediatric and adult patients 19,20 looked at 12-month changes in our natural history patients. These data, even if limited by the fact that there were repeated measures from the same patients, allowed us to provide additional information on the possibility to see stability or meaningful changes within each subgroup.…”

Section: Discussionmentioning

confidence: 99%

“…It is, therefore, important to gather more information on the natural history of SMA type III for the interpretation of the realworld data that are increasingly becoming available. [19][20][21][22] The aim of this study was to describe the natural history in a large cohort of patients with SMA type III assessed longitudinally using the Hammersmith Functional Motor Scale Expanded (HFMSE). 23 More specifically, we were interested in establishing the distribution of scores at different ages, and the possible patterns of progression in patients with SMA types IIIA and IIIB.…”

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confidence: 99%

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Clinical Variability in Spinal Muscular Atrophy Type III

Coratti

Messina

Lucibello

et al. 2020

Annals of Neurology

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Objective: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status. Methods: HFMSE longitudinal changes were assessed using piecewise linear mixed-effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured View this article online at wileyonlinelibrary.com.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Clinical Variability in Spinal Muscular Atrophy Type III

Coratti

Messina

Lucibello

et al. 2020

Annals of Neurology

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“…A combinantion treatment of SMA cells with LBH589 and an antisense oligonucleotide that mimic Nusinersen (ASO_ISSN1) produced additive effects on SMN2 splicing and SMN protein expression (Pagliarini et al, 2019). Nusinersen, an anitisense oligonucleotide, has been recently approved by the US FDA for treatment of SMA (Hagenacker et al, 2020).…”

Section: Effects Of Hdaci In Various Neurodegenerative Disorders Modementioning

confidence: 99%

Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation

2020

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Histone deacetylases (HADC) are the enzymes that remove acetyl group from lysine residue of histones and non-histone proteins and regulate the process of transcription by binding to transcription factors and regulating fundamental cellular process such as cellular proliferation, differentiation and development. In neurodegenerative diseases, the histone acetylation homeostasis is greatly impaired, shifting towards a state of hypoacetylation. The histone hyperacetylation produced by direct inhibition of HDACs leads to neuroprotective actions. This review attempts to elaborate on role of small molecule inhibitors of HDACs on neuronal differentiation and throws light on the potential of HDAC inhibitors as therapeutic agents for treatment of neurodegenerative diseases. The role of HDACs in neuronal cellular and disease models and their modulation with HDAC inhibitors are also discussed. Significance of these HDAC inhibitors has been reviewed on the process of neuronal differentiation, neurite outgrowth and neuroprotection regarding their potential therapeutic application for treatment of neurodegenerative diseases.

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“…In adult SMA patients, controlled studies in larger patients groups assessing the efficacy of nusinersen with suitable outcome measures have not been conducted. A recently published observational study in a large cohort of nusinersen treated adults demonstrated significant improvements in the Hammersmith Functional Motor Scale Expanded (HFMSE) under nusinersen treatment [11]. Because of floor and ceiling effects in commonly used motor scores, and for monitoring of changes in motor-related symptoms such as ventilation and swallowing, patient-reported outcomes (PROs) have been discussed as an important additional outcome to assess treatment efficacy, especially in severely affected adult patients, in which common motor function tests are not applicable [11,12].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Treatment expectations and patient-reported outcomes of nusinersen therapy in adult spinal muscular atrophy

et al. 2020

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Background The antisense-oligonucleotide (ASO) nusinersen has recently been approved as the first genetically modifying therapy for 5q-associated spinal muscular atrophy (SMA) based on randomized sham-controlled trials in infants and children. The efficacy in adults with long disease history and advanced disease status is still widely unknown; the same applies to specific expectations of adult SMA patients and to what extent they are met and may impact outcome measures. Methods In a longitudinal monocentric study in adult patients with SMA types 2-4, the Stanford Expectations of Treatment Scale (SETS) was assessed prior to and during nusinersen treatment. Treatment outcome was evaluated using patient-reported outcomes (PROs) as well as objectively quantifiable motor outcome measures. Results Adult SMA patients had high expectations of nusinersen treatment effectiveness regarding increase in muscle strength and disease stabilization. Via PROs, 75% stated improvements in muscle strength, endurance and independence under therapy which was in line with slight improvements in quantifiable motor scores during a ten month observation period. In contrast, patients only expressed few negative expectations which further decreased during therapy. Conclusions This study showed mainly positive treatment expectations and PROs in patients undergoing nusinersen treatment along with measurable functional improvement in adult SMA patients. Moreover, treatment expectations did not significantly influence outcome measures. Keywords Spinal muscular atrophy (SMA) • Patient-reported outcomes (PROs) • Stanford expectations of treatment scale (SETS) • Nusinersen • Antisense-oligonucleotide (ASO)

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Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study

Cited by 249 publications

References 20 publications

Clinical Variability in Spinal Muscular Atrophy Type III

Clinical Variability in Spinal Muscular Atrophy Type III

Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation

Treatment expectations and patient-reported outcomes of nusinersen therapy in adult spinal muscular atrophy

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