{
  "abstract": "Background Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by survival motor neuron (SMN1) deletion. While loss of ambulation in SMA type III typically occurs at a median age of 13.4 years, outcomes in the treatment era remain unclear. This study aims to address that gap by investigating ambulation outcomes in individuals with type III receiving disease-modifying therapies.Methods This retrospective study analysed prospectively collected international data. Time-dependent Cox models assessed the association between treatment initiation and age at loss of ambulation, adjusting for age at onset, sex, SMN2 copies, birth year and country. Treatment was modelled as a time-dependent covariate to avoid immortal time bias. Descriptive analyses used Mann-Whitney U and χ² tests.Results Among 555 individuals with type III, treatment halved the risk of ambulation loss (HR=0.50), with median loss at 44 vs 32 years in treated and untreated groups. Later onset, ≥4 SMN2 copies and female sex were also protective. The treatment effect was significant in type IIIA (HR=0.34) but not IIIB, with no significant interactions by sex, country or SMN2, though effects remained directionally protective.Conclusions Treatment in type III reduced the risk of ambulation loss by 50%, extending median ambulation by 12 years, with the greatest benefit in type IIIA. Later onset, female sex and higher SMN2 copy number were also protective but did not modify treatment effect. These findings underscore the value of early treatment and support its broad use to preserve ambulation across clinical subgroups.",
  "authors": [
    {
      "affiliations": [
        "Pediatric Neurology, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy",
        "Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy"
      ],
      "name": "Giorgia Coratti"
    },
    {
      "affiliations": [
        "University of Genoa, Genoa, Italy"
      ],
      "name": "Francesca Bovis"
    },
    {
      "affiliations": [
        "Centro Clinico NeMO, Milan, Italy"
      ],
      "name": "Valentina Franchino"
    },
    {
      "affiliations": [
        "Columbia University, New York, New York, USA"
      ],
      "name": "Jacqueline Montes"
    },
    {
      "affiliations": [
        "Centro Clinico NeMO, Milan, Italy"
      ],
      "name": "Valeria Ada Sansone"
    },
    {
      "affiliations": [
        "Stanford University, Stanford, California, USA"
      ],
      "name": "Sally Dunaway Young"
    },
    {
      "affiliations": [
        "Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy"
      ],
      "name": "Chiara Cutrì"
    },
    {
      "affiliations": [
        "Children’s Hospital Boston, Boston, Massachusetts, USA"
      ],
      "name": "Amy Pasternak"
    },
    {
      "affiliations": [
        "Pediatric Neurology, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy",
        "Department of Medicine and Surgery, University of Parma, Parma, Italy"
      ],
      "name": "Maria Carmela Pera"
    },
    {
      "affiliations": [
        "Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy"
      ],
      "name": "Marika Pane"
    },
    {
      "affiliations": [
        "Department of Physical Therapy, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"
      ],
      "name": "Allan Glanzman"
    },
    {
      "affiliations": [
        "Department of Neurosciences, University of Padua, Padua, Italy"
      ],
      "name": "Elena Pegoraro"
    },
    {
      "affiliations": [
        "Stanford University, Stanford, California, USA"
      ],
      "name": "Tina Duong"
    },
    {
      "affiliations": [
        "Department of Neurosciences, University of Padua, Padua, Italy"
      ],
      "name": "Elena Sogus"
    },
    {
      "affiliations": [
        "Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"
      ],
      "name": "Maria Sframeli"
    },
    {
      "affiliations": [
        "Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"
      ],
      "name": "Sonia Messina"
    },
    {
      "affiliations": [
        "Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK",
        "National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, London, UK"
      ],
      "name": "Elzo Cavalcante"
    },
    {
      "affiliations": [
        "Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK",
        "National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, London, UK"
      ],
      "name": "Maria Cristina Scoto"
    },
    {
      "affiliations": [
        "Neurosciences, Bambino Gesu Pediatric Hospital IRCCS, Rome, Italy"
      ],
      "name": "Adele D’Amico"
    },
    {
      "affiliations": [
        "Columbia University, New York, New York, USA"
      ],
      "name": "Rafael Rodriguez-Torres"
    },
    {
      "affiliations": [
        "Department of Neurosciences, Università degli Studi di Torino, Turin, Italy"
      ],
      "name": "Tiziana Mongini"
    },
    {
      "affiliations": [
        "Foundation IRCCS Carlo Besta Neurological Institute, Milano, Italy"
      ],
      "name": "Lorenzo Maggi"
    },
    {
      "affiliations": [
        "Centro Clinico NeMO, Ancona, Italy"
      ],
      "name": "Michela Coccia"
    },
    {
      "affiliations": [
        "Department of Clinical and Experimental Sciences, NeMO-Brescia Clinical Center for Neuromuscular Diseases, University of Brescia, Brescia, Italy"
      ],
      "name": "Massimiliano Filosto"
    },
    {
      "affiliations": [
        "Centro Clinico NeMO, Trento, Italy"
      ],
      "name": "Riccardo Zuccarino"
    },
    {
      "affiliations": [
        "Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"
      ],
      "name": "Riccardo Masson"
    },
    {
      "affiliations": [
        "Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy"
      ],
      "name": "Giulia Ricci"
    },
    {
      "affiliations": [
        "Center of Translational and Experimental Myology and Department of Neuroscience, Rehabilitation, Ophthalmology Genetics, Maternal and Child Health, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Claudio Bruno"
    },
    {
      "affiliations": [
        "Department of Neurosciences and Reproductive and Odontostomatologic Sciences, Federico II University Hospital, Naples, Italy"
      ],
      "name": "Lucia Ruggiero"
    },
    {
      "affiliations": [
        "IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy",
        "Centro Clinico NeMO, Bologna, Italy"
      ],
      "name": "Veria Vacchiano"
    },
    {
      "affiliations": [
        "Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy"
      ],
      "name": "Eustachio D’errico"
    },
    {
      "affiliations": [
        "Neurology Unit, Department of Neurosciences, University Hospital Santa Maria della Misericordia, Udine, Italy"
      ],
      "name": "Lorenzo Verriello"
    },
    {
      "affiliations": [
        "Department of Precision Medicine, University of Campania Luigi Vanvitelli, Caserta, Italy"
      ],
      "name": "Vincenzo Nigro"
    },
    {
      "affiliations": [
        "IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy"
      ],
      "name": "Gaia Scarpini"
    },
    {
      "affiliations": [
        "Neurology Mental Health and Sensory Organs (NESMOS), University of Rome La Sapienza, Rome, Italy",
        "Institut de Myologie, Paris, France"
      ],
      "name": "Matteo Garibaldi"
    },
    {
      "affiliations": [
        "Department of Neurology/Stroke Unit, Ospedale di Bolzano, Bolzano, Italy"
      ],
      "name": "Mara Turri"
    },
    {
      "affiliations": [
        "Ospedale Pediatrico Meyer, Florence, Italy"
      ],
      "name": "Chiara Ticci"
    },
    {
      "affiliations": [
        "Department of Child Neuropsychiatry, Fondazione Istituto Neurologico Nazionale Casimiro Mondino, Pavia, Italy"
      ],
      "name": "Angela Berardinelli"
    },
    {
      "affiliations": [
        "Padua University Hospital, Padua, Italy"
      ],
      "name": "Caterina Agosto"
    },
    {
      "affiliations": [
        "SC Neuropsichiatria Infantile, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino, Torino, Italy"
      ],
      "name": "Federica Ricci"
    },
    {
      "affiliations": [
        "The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"
      ],
      "name": "Zarazuela Zolkipli-Cunningham"
    },
    {
      "affiliations": [
        "Children’s Hospital Boston, Boston, Massachusetts, USA"
      ],
      "name": "Basil T Darras"
    },
    {
      "affiliations": [
        "Stanford University, Stanford, California, USA"
      ],
      "name": "John Day"
    },
    {
      "affiliations": [
        "Neurology Department, Columbia University, New York, New York, USA"
      ],
      "name": "Michio Hirano"
    },
    {
      "affiliations": [
        "Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK",
        "National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, London, UK"
      ],
      "name": "Francesco Muntoni"
    },
    {
      "affiliations": [
        "Pediatrics, St Jude Children’s Research Hospital, Memphis, Tennessee, USA"
      ],
      "name": "Richard S Finkel"
    },
    {
      "affiliations": [
        "Pediatric Neurology, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy",
        "Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy"
      ],
      "name": "Eugenio Mercuri"
    },
    {
      "affiliations": [],
      "name": "On behalf of the international SMA consortium (ISMAC)"
    }
  ],
  "title": "Loss of ambulation in SMA III at the time of disease-modifying treatments: an international study",
  "uid": "3e3ec943-2949-5238-b962-aef5ce999243"
}