PLoS ONE (Jan 2013)

SMA-MAP: a plasma protein panel for spinal muscular atrophy.

  • Dione T Kobayashi,
  • Jing Shi,
  • Laurie Stephen,
  • Karri L Ballard,
  • Ruth Dewey,
  • James Mapes,
  • Brett Chung,
  • Kathleen McCarthy,
  • Kathryn J Swoboda,
  • Thomas O Crawford,
  • Rebecca Li,
  • Thomas Plasterer,
  • Cynthia Joyce,
  • Biomarkers for Spinal Muscular Atrophy Study Group,
  • Wendy K Chung,
  • Petra Kaufmann,
  • Basil T Darras,
  • Richard S Finkel,
  • Douglas M Sproule,
  • William B Martens,
  • Michael P McDermott,
  • Darryl C De Vivo,
  • Pediatric Neuromuscular Clinical Research Network,
  • Michael G Walker,
  • Karen S Chen

DOI
https://doi.org/10.1371/journal.pone.0060113
Journal volume & issue
Vol. 8, no. 4
p. e60113

Abstract

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OBJECTIVESSpinal Muscular Atrophy (SMA) presents challenges in (i) monitoring disease activity and predicting progression, (ii) designing trials that allow rapid assessment of candidate therapies, and (iii) understanding molecular causes and consequences of the disease. Validated biomarkers of SMA motor and non-motor function would offer utility in addressing these challenges. Our objectives were (i) to discover additional markers from the Biomarkers for SMA (BforSMA) study using an immunoassay platform, and (ii) to validate the putative biomarkers in an independent cohort of SMA patients collected from a multi-site natural history study (NHS).METHODSBforSMA study plasma samples (N = 129) were analyzed by immunoassay to identify new analytes correlating to SMA motor function. These immunoassays included the strongest candidate biomarkers identified previously by chromatography. We selected 35 biomarkers to validate in an independent cohort SMA type 1, 2, and 3 samples (N = 158) from an SMA NHS. The putative biomarkers were tested for association to multiple motor scales and to pulmonary function, neurophysiology, strength, and quality of life measures. We implemented a Tobit model to predict SMA motor function scores.RESULTS12 of the 35 putative SMA biomarkers were significantly associated (pCONCLUSIONSDiscovery and validation using independent cohorts yielded a set of SMA biomarkers significantly associated with motor function and other measures of SMA disease activity. A commercial SMA-MAP biomarker panel was generated for further testing in other SMA collections and interventional trials. Future work includes evaluating the panel in other neuromuscular diseases, for pharmacodynamic responsiveness to experimental SMA therapies, and for predicting functional changes over time in SMA patients.