Spinal Muscular Atrophies of Childhood/complications/epidemiology/physiopathology; Young Adult
Abstract :
[en] Spinal muscular atrophy (SMA) is a monogenic disorder caused by loss of function mutations in the survival motor neuron 1 gene, which results in a broad range of disease severity, from neonatal to adult onset. There is currently a concerted effort to define the natural history of the disease and develop outcome measures that accurately capture its complexity. As several therapeutic strategies are currently under investigation and both the FDA and EMA have recently approved the first medical treatment for SMA, there is a critical need to identify the right association of responsive outcome measures and biomarkers for individual patient follow-up. As an approved treatment becomes available, untreated patients will soon become rare, further intensifying the need for a rapid, prospective and longitudinal study of the natural history of SMA Type 2 and 3. Here we present the baseline assessments of 81 patients aged 2 to 30 years of which 19 are non-sitter SMA Type 2, 34 are sitter SMA Type 2, 9 non-ambulant SMA Type 3 and 19 ambulant SMA Type 3. Collecting these data at nine sites in France, Germany and Belgium established the feasibility of gathering consistent data from numerous and demanding assessments in a multicenter SMA study. Most assessments discriminated between the four groups well. This included the Motor Function Measure (MFM), pulmonary function testing, strength, electroneuromyography, muscle imaging and workspace volume. Additionally, all of the assessments showed good correlation with the MFM score. As the untreated patient population decreases, having reliable and valid multi-site data will be imperative for recruitment in clinical trials. The pending two-year study results will evaluate the sensitivity of the studied outcomes and biomarkers to disease progression. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02391831).
Disciplines :
Pediatrics Neurology
Author, co-author :
Chabanon, Aurelie; Institute of Myology, GH Pitié-Salpêtrière, Paris, France
Seferian, Andreea Mihaela; Institute of Myology, GH Pitié Salpêtrière, Paris, France
DARON, Aurore ; Centre Hospitalier Universitaire de Liège - CHU > Département de Pédiatrie > Service de pédiatrie
Pereon, Yann; Centre de Référence Maladies Neuromusculaires Atlantique-Occitanie-Caraïbes, Hopital Hôtel-Dieu, Nantes, France
Cances, Claude; Centre de Référence des Maladies Neuromusculaires, Hôpital des Enfants, Toulouse, France
Vuillerot, Carole; Service de rééducation pédiatrique infantile ºL'Escaleº, Hôpital Mère Enfant, CHU Lyon, France
De Waele, Liesbeth; Department of Pediatric Neurology, University Hospitals Leuven, Belgium
Cuisset, Jean-Marie; Centre de Référence des Maladies Neuromusculaires, Hôpital Roger Salengro, Lille, France
Laugel, Vincent; Neuropédiatrie/INSERM CIC 1434, CHU Strasbourg Hautepierre, Strasbourg, France
Schara, Ulrike; Paediatric neurology and neuromuscular center, University of Essem, Germany
Gidaro, Teresa; Institute of Myology, GH Pitié Salpêtrière, Paris, France
Gilabert, Stephanie; Institute of Myology, GH Pitié Salpêtrière, Paris, France
Hogrel, Jean-Yves; Institute of Myology, GH Pitié Salpêtrière, Paris, France
Baudin, Pierre-Yves; Consultants for Research in Imaging and Spectroscopy (CRIS), Tournai, Belgium
Carlier, Pierre; Institute of Myology, GH Pitié Salpêtrière, Paris, France
Fournier, Emmanuel; Institute of Myology, GH Pitié Salpêtrière, Paris, France
Lowes, Linda Pax; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA
Hellbach, Nicole; Roche Pharmaceutical Research and Early Development, Roche Innovation Center, Basel, Switzerland
Seabrook, Timothy; Roche Pharmaceutical Research and Early Development, Roche Innovation Center, Basel, Switzerland
Toledano, Elie; Institut Roche, Paris, France
Annoussamy, Melanie; Institute of Myology, GH Pitié Salpêtrière, Paris, France
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques > Neuropédiatrie
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