title: SMA-MAP: a plasma protein panel for spinal muscular atrophy.
abstract: OBJECTIVE
  Spinal 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).
  
  
  METHODS
  BforSMA 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.
  
  
  RESULTS
  12 of the 35 putative SMA biomarkers were significantly associated (p<0.05) with motor function, with a 13(th) analyte being nearly significant. Several other analytes associated with non-motor SMA outcome measures. From these 35 biomarkers, 27 analytes were selected for inclusion in a commercial panel (SMA-MAP) for association with motor and other functional measures.
  
  
  CONCLUSIONS
  Discovery 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.
authors.affiliation: Spinal Muscular Atrophy Foundation, New York, New York, United States of America. dkobayashi@smafoundation.org
authors.forename: Dione T
authors.initials: DT
authors.lastname: Kobayashi
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Laurie
authors.initials: L
authors.lastname: Stephen
authors.forename: Karri L
authors.initials: KL
authors.lastname: Ballard
authors.forename: Ruth
authors.initials: R
authors.lastname: Dewey
authors.forename: James
authors.initials: J
authors.lastname: Mapes
authors.forename: Brett
authors.initials: B
authors.lastname: Chung
authors.forename: Kathleen
authors.initials: K
authors.lastname: McCarthy
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Swoboda
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Crawford
authors.forename: Rebecca
authors.initials: R
authors.lastname: Li
authors.forename: Thomas
authors.initials: T
authors.lastname: Plasterer
authors.forename: Cynthia
authors.initials: C
authors.lastname: Joyce
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Petra
authors.initials: P
authors.lastname: Kaufmann
authors.forename: Basil T
authors.initials: BT
authors.lastname: Darras
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finkel
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Sproule
authors.forename: William B
authors.initials: WB
authors.lastname: Martens
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDermott
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
authors.forename: Michael G
authors.initials: MG
authors.lastname: Walker
authors.forename: Karen S
authors.initials: KS
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D013058:Mass Spectrometry; D008875:Middle Aged; D009043:Motor Activity; D009134:Muscular Atrophy, Spinal / Q000097:blood* / Q000175:diagnosis; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D011933:Reagent Kits, Diagnostic
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