Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study

PLoS One. 2018 Jul 26;13(7):e0201004. doi: 10.1371/journal.pone.0201004. eCollection 2018.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Longitudinal Studies
  • Lung / physiopathology
  • Male
  • Muscle Strength
  • Muscle Weakness / complications
  • Psychomotor Performance
  • Spinal Muscular Atrophies of Childhood / complications
  • Spinal Muscular Atrophies of Childhood / epidemiology*
  • Spinal Muscular Atrophies of Childhood / physiopathology
  • Young Adult

Associated data

  • ClinicalTrials.gov/NCT02391831

Grant support

The NatHis-SMA study is co-funded by Institut Roche and Association Institut de Myologie. Both funders played a role in the study design, data analysis, decision to publish and preparation of the manuscript. Among the authors, Nicole Hellbach, Timothy Seabrook and Elie Toledano are employees of the F. Hoffmann-La Roche group, whereas Pierre-Yves Baudin is employee of Consultants for Research in Imaging and Spectroscopy (CRIS). We confirm these authors contributions reflects the respective roles they had in the study.