Natural history of Type 2 and 3 spinal muscular atrophy: 2‐year NatHis‐SMA study

Annoussamy, M.; Seferian, A.; Daron, Aurore; Péreón, Yann; Cancés, Claude; Vuillerot, Carole; Waele, Liesbeth De; Laugel, Vincent; Schara, Ulrike; Gidaro, T.; Lilien, C.; Hogrel, Jean‐Yves; Carlier, Pierre; Fournier, Emmanuel; Lowes, Linda; Gorni, Ksenija; Moal, Myriam Ly‐Le; Hellbach, Nicole; Seabrook, Timothy J.; Czech, Christian; Hermosilla, Ricardo; Servais, Laurent

doi:10.1002/acn3.51281

Cited by 77 publications

(83 citation statements)

References 38 publications

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“…Qualitative gait analysis as stride length and velocity were mostly obtained based on evaluations inside clinical facilities [ 25 , 26 ]. Recently, several efforts were made to collect, in a home-based setting, qualitative data from subjects with various diseases and control populations [ 18 , 19 , 22 , 27 ]. However, to the best of our knowledge, we found no other published data regarding normative longitudinal evaluations of spontaneous stride velocity, stride length, and walking activity in an everyday setting.…”

Section: Discussionmentioning

confidence: 99%

“…Additional data are needed to qualify the measure as a primary endpoint [ 16 ]. Wearable technology is or has been used in clinical trials of therapies for spinal muscular atrophy [ 18 , 19 ], facioscapulohumeral muscular dystrophy (NCT02579239, NCT04004000), limb girdle muscular dystrophy type 2E (NCT02579239), centronuclear myopathy (NCT02057705), and Angelman syndrome (NCT04259281).…”

Section: Introductionmentioning

confidence: 99%

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Normative data on spontaneous stride velocity, stride length, and walking activity in a non-controlled environment

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Ulinici

Daron

et al. 2021

Orphanet J Rare Dis

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Background Normative data are necessary for validation of new outcome measures. Recently, the 95th centile of stride speed was qualified by the European Medicines Agency as a valid secondary outcome for clinical trials in subjects with Duchenne muscular dystrophy. This study aims to obtain normative data on spontaneous stride velocity and length in a non-controlled environment and their evolution after 12 months. Method Ninety-one healthy volunteers (50 females, 41 males), with a mean age of 16 years and 2 months, were recruited and assessed at baseline and 12 months later. The 4-stair climb, 6-min walk test, 10-m walk test and rise from floor assessments were performed. Stride length, stride velocity, and the distance walked per hour were studied in an everyday setting for one month after each evaluation. Results Of the 91 subjects assessed, 82 provided more than 50 h of recordings at baseline; and 73 subjects provided the same at the end of the year. We observed significant positive correlations of the stride length with age and height of participants, and a significant increase of the median stride length in children after the period. In this group, the 95th centile stride velocity was not correlated with age and was stable after one year. All measures but the 10MWT were stable in adults after a one-year period. Conclusion This study provides with data on the influence of age, height, and gender on stride velocity and length as well as accounting for natural changes after one year in controls.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Normative data on spontaneous stride velocity, stride length, and walking activity in a non-controlled environment

Poleur

Ulinici

Daron

et al. 2021

Orphanet J Rare Dis

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“…Based on EMA-defined precision requirements, the wearable sensor Ac�Myo® is currently the only suitable and validated device for gathering SV95C data for use in clinical trials. Other Ac�Myo® acquired endpoints are likely to be developed and validated in both ambulatory and non-ambulatory neuromuscular diseases [21,22]. The Clinician's Perspective Clinicians are acutely aware of the need for outcome measures for DMD and other neuromuscular diseases that can accurately assess "typical daily function" across a diverse spectrum of patients.…”

Section: What Is Ac�myo®?mentioning

confidence: 99%

“…What is ActiMyo ® ? Description of the ActiMyo ® device and its validation for gathering SV95C data[20][21][22]. SV95C, stride velocity 95th centile.…”

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confidence: 99%

First Regulatory Qualification of a Novel Digital Endpoint in Duchenne Muscular Dystrophy: A Multi-Stakeholder Perspective on the Impact for Patients and for Drug Development in Neuromuscular Diseases

et al. 2021

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Background: Functional outcome measures used to assess efficacy in clinical trials of investigational treatments for rare neuromuscular diseases like Duchenne muscular dystrophy (DMD) are performance-based tasks completed by the patient during hospital visits. These are prone to bias and may not reflect motor abilities in real-world settings. Digital tools, such as wearable devices and other remote sensors, provide the opportunity for continuous, objective, and sensitive measurements of functional ability during daily life. Maintaining ambulation is of key importance to individuals with DMD. Stride velocity 95th centile (SV95C) is the first wearable acquired digital endpoint to receive qualification from the European Medicines Agency (EMA) to quantify the ambulation ability of ambulant DMD patients aged ≥5 years in drug therapeutic studies; it is also currently under review for the US Food and Drug Administration (FDA) qualification. Summary: Focusing on SV95C as a key example, we describe perspectives of multiple stakeholders on the promise of novel digital endpoints in neuromuscular disease drug development.

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“…86 In natural history studies, the pattern of disease progression in types 2 and 3 SMA also typically depends on age. 70,71,73,74,87 Younger age groups experience gains in motor function. The steepest declines in motor function occur during adolescence as weight is gained, and contractures and scoliosis develop.…”

Section: Factors Affecting Motor Functionmentioning

confidence: 99%

Prognostic Factors and Treatment‐Effect Modifiers in Spinal Muscular Atrophy

Baranello

Gorni

Daigl

et al. 2021

Clin Pharma and Therapeutics

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Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with type 1 SMA do not achieve major motor milestones, and death from respiratory failure typically occurs before 2 years of age. Individuals with types 2 and 3 SMA exhibit milder phenotypes and have better functional and survival outcomes. Herein, a systematic literature review was conducted to identify factors that influence the prognosis of types 1, 2, and 3 SMA. In untreated infants with type 1 SMA, absence of symptoms at birth, a later symptom onset, and a higher survival of motor neuron 2 ( SMN2 ) copy number are all associated with increased survival. Disease duration, age at treatment initiation, and, to a lesser extent, baseline function were identified as potential treatment‐modifying factors for survival, emphasizing that early treatment with disease‐modifying therapies (DMT) is essential in type 1 SMA. In patients with types 2 and 3 SMA, factors considered prognostic of changes in motor function were SMN2 copy number, age, and ambulatory status. Individuals aged 6–15 years were particularly vulnerable to developing complications (scoliosis and progressive joint contractures) which negatively influence functional outcomes and may also affect the therapeutic response in patients. Age at the time of treatment initiation emerged as a treatment‐effect modifier on the outcome of DMTs. Factors identified in this review should be considered prior to designing or analyzing studies in an SMA population, conducting population matching, or summarizing results from different studies on the treatments for SMA.

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Natural history of Type 2 and 3 spinal muscular atrophy: 2‐year NatHis‐SMA study

Cited by 77 publications

References 38 publications

Normative data on spontaneous stride velocity, stride length, and walking activity in a non-controlled environment

Normative data on spontaneous stride velocity, stride length, and walking activity in a non-controlled environment

First Regulatory Qualification of a Novel Digital Endpoint in Duchenne Muscular Dystrophy: A Multi-Stakeholder Perspective on the Impact for Patients and for Drug Development in Neuromuscular Diseases

Prognostic Factors and Treatment‐Effect Modifiers in Spinal Muscular Atrophy

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