Journal article
SMA-MAP: a plasma protein panel for spinal muscular atrophy
PloS one, Vol.8(4), pp.e60113-e60113
2013
DOI: 10.1371/journal.pone.0060113
PMCID: PMC3615018
PMID: 23565191
Abstract
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).
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.
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.
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.
Details
- Title: Subtitle
- SMA-MAP: a plasma protein panel for spinal muscular atrophy
- Creators
- Dione T Kobayashi - Spinal Muscular Atrophy Foundation, New York, New York, United States of America. dkobayashi@smafoundation.orgJing ShiLaurie StephenKarri L BallardRuth DeweyJames MapesBrett ChungKathleen McCarthyKathryn J SwobodaThomas O CrawfordRebecca LiThomas PlastererCynthia JoyceWendy K ChungPetra KaufmannBasil T DarrasRichard S FinkelDouglas M SprouleWilliam B MartensMichael P McDermottDarryl C De VivoMichael G WalkerKaren S Chen - Spinal Muscular Atrophy FoundationBiomarkers for Spinal Muscular Atrophy Study GroupPediatric Neuromuscular Clinical Research Network
- Contributors
- Katherine D Mathews (Contributor) - University of Iowa, Stead Family Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.8(4), pp.e60113-e60113
- DOI
- 10.1371/journal.pone.0060113
- PMID
- 23565191
- PMCID
- PMC3615018
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- P30 HD018655 / NICHD NIH HHS R01 HD069045 / NICHD NIH HHS R01 HD054599 / NICHD NIH HHS
- Language
- English
- Date published
- 2013
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984070329202771
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