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

被引：73

作者：

Annoussamy, Melanie ^{[1
,2
]}

Seferian, Andreea M. ^{[1
]}

Daron, Aurore ^{[3
]}

Pereon, Yann ^{[4
]}

Cances, Claude ^{[5
,6
]}

Vuillerot, Carole ^{[7
,8
]}

De Waele, Liesbeth ^{[9
,10
]}

Laugel, Vincent ^{[11
]}

Schara, Ulrike ^{[12
]}

Gidaro, Teresa ^{[1
]}

Lilien, Charlotte ^{[1
,13
]}

Hogrel, Jean-Yves ^{[1
]}

Carlier, Pierre ^{[1
]}

Fournier, Emmanuel ^{[1
]}

Lowes, Linda ^{[14
]}

Gorni, Ksenija ^{[15
]}

Ly-Le Moal, Myriam ^{[16
]}

Hellbach, Nicole ^{[17
]}

Seabrook, Timothy ^{[17
]}

Czech, Christian ^{[17
,18
]}

Hermosilla, Ricardo ^{[17
]}

Servais, Laurent ^{[1
,13
,19
,20
]}

机构：

[1] GH Pitie Salpetriere, Inst Myol, Paris, France

[2] Sysnav, Vernon, France

[3] CHU Liege, Ctr Reference Malad Neuromusculaires, Liege, Belgium

[4] Hop Hotel Dieu, Ctr Reference Malad Neuromusculaires Atlantique O, Nantes, France

[5] Hop Enfants, Ctr Reference Malad, Neuromusculaires, Toulouse, France

[6] Hop Enfants, Unite Neurol Pediat, Toulouse, France

[7] CHU Lyon, Serv Reeduc Pediat Infantile LEscale, Hop Mere Enfant, Bron, France

[8] Univ Lyon, CNRS, Neuromyogen Inst, UMR 5310 INSERM U1217, Lyon, France

[9] Univ Hosp Leuven, Dept Pediat Neurol, Leuven, Belgium

[10] KU Leuven Kulak Kortrijk, Dept Dev & Regenerat, Kortrijk, Belgium

[11] CHU Strasbourg Hautepierre, Neuropediat, INSERM CIC 1434, Strasbourg, France

[12] Univ Essen Gesamthsch, Paediat Neurol & Neuromuscular Ctr, Essen, Germany

[13] Univ Oxford, Dept Paediat, MDUK Oxford Neuromuscular Ctr, Oxford, England

[14] Nationwide Childrens Hosp, Ctr Gene Therapy, Columbus, OH USA

[15] F Hoffmann La Roche Ltd, PDMA Neurosci & Rare Dis, Basel, Switzerland

[16] Inst Roche, Boulogne, France

[17] Roche Innovat Ctr, Roche Pharmaceut Res & Early Dev, Basel, Switzerland

[18] Pfizer, Rare Dis Res Unit, Nice, France

[19] Univ Hosp Liege, Div Child Neurol, Ctr References Malad Neuromusculaires, Dept Pediat, Liege, Belgium

[20] Univ Liege, Liege, Belgium

来源：

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY | 2021年 / 8卷 / 02期

关键词：

NASAL INSPIRATORY PRESSURE; VALUES;

D O I：

10.1002/acn3.51281

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: To characterize the natural history of spinal muscular atrophy (SMA) over 24 months using innovative measures such as wearable devices, and to provide evidence for the sensitivity of these measures to determine their suitability as endpoints in clinical trials. Methods: Patients with Type 2 and 3 SMA (N = 81) with varied functional abilities (sitters, nonsitters, nonambulant, and ambulant) who were not receiving disease-modifying treatment were assessed over 24 months: motor function (Motor Function Measure [MFM]), upper limb strength (MyoGrip, MyoPinch), upper limb activity (ActiMyo (R)), quantitative magnetic resonance imaging (fat fraction [FFT2] mapping and contractile cross-sectional area [C-CSA]), pulmonary function (forced vital capacity [FVC], peak cough flow, maximum expiratory pressure, maximum inspiratory pressure, and sniff nasal inspiratory pressure), and survival of motor neuron (SMN) protein levels. Results: MFM32 scores declined significantly over 24 months, but not 12 months. Changes in upper limb activity could be detected over 6 months and continued to decrease significantly over 12 months, but not 24 months. Upper limb strength decreased significantly over 12 and 24 months. FVC declined significantly over 12 months, but not 24 months. FFT2 increased over 12 and 24 months, although not with statistical significance. A significant increase in C-CSA was observed at 12 but not 24 months. Blood SMN protein levels were stable over 12 and 24 months. Interpretation: These data demonstrate that the MFM32, MyoGrip, MyoPinch, and ActiMyo (R) enable the detection of a significant decline in patients with Type 2 and 3 SMA over 12 or 24 months.

引用

页码：359 / 373

页数：15