Candidate Proteins, Metabolites and Transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study - Discovery platforms identify 200 candidate biomarkers associated with disease severity

Sep 3, 2026

Upload by McQueen

Spinal Muscular Atrophy (SMA) is a neurodegenerative motor neuron disorder caused by homozygous SMN1 mutation, with disease severity inversely related to SMN2 copy number. To support clinical trial design and therapeutic target discovery, a cross-sectional evaluation of genetically confirmed SMA children assessed novel biomarkers using unbiased proteomic, metabolomic, and transcriptomic platforms. In 108 children and 22 controls, 200 candidate biomarkers correlated with Modified Hammersmith Functional Motor Scale scores, while no transcripts showed association. Protein and metabolite candidates warrant further prospective validation.

LanguageEnglish

CategoryGeneral

FormatPDF

Pages17

Reading Time6 min

AccessFree to download

Background

Rationale for biomarker identification

Objective

Materials and Methods

Study design and participants

Discovery platforms and severity measures

Results

Biomarker counts and correlations

Transcript analysis

Discussion

Key findings and future work

| Abstract
Background: Spinal Muscular Atrophy (SMA) is a neurodegenerative motor neuron disorder resulting from a homozygous mutation of the survival of motor neuron 1 (SMN1) gene. The gene product, SMN protein, functions in RNA biosynthesis in all tissues. In humans, a nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing a small amount of full-length SMN protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify novel therapeutic targets.
Objective:: To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches.
Materials and Methods:: A cross-sectional single evaluation was performed in 108 children with genetically confirmed SMA, aged 2–12 years, manifesting a broad range of disease severity and selected to distinguish factors associated with SMA type and present functional ability independent of age. Blood and urine specimens from these and 22 age-matched healthy controls were interrogated using proteomic, metabolomic and transcriptomic discovery platforms. Analyte associations were evaluated against a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS) and to a number of secondary clinical measures.
Results: A total of 200 candidate biomarkers correlate with MHFMS scores: 97 plasma proteins, 59 plasma metabolites (9 amino acids, 10 free fatty acids, 12 lipids and 28 GC/MS metabolites) and 44 urine metabolites. No transcripts correlated with MHFMS.
Discussion: In this cross-sectional study,‘‘BforSMA’’(Biomarkers for SMA), candidate protein and metabolite markers were identified. No transcript biomarker candidates were identified. Additional mining of this rich dataset may yield important insights into relevant SMA-related pathophysiology and biological network associations. Additional prospective studies are needed to confirm these findings, demonstrate sensitivity to change with disease progression, and assess potential impact on clinical trial design.
[Trial Registry:](Trial Registry: Clinicaltrials.gov)[ Clinicaltrials.gov](Trial Registry: Clinicaltrials.gov) NCT00756821. | | --- | | Citation: Finkel RS, Crawford TO, Swoboda KJ, Kaufmann P, Juhasz P, et al. (2012) Candidate Proteins, Metabolites and Transcripts in the Biomarkers for Spinal
Muscular Atrophy (BforSMA) Clinical Study. PLoS ONE 7(4): e35462 . doi:10.1371/journal.pone.0035462
Editor: Christoph Winkler, National University of Singapore, Singapore
Received May 23, 2011; Accepted March 19, 2012; Published April 27, 2012
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Funding: This study was sponsored by the Spinal Muscular Atrophy (SMA) Foundation, New York, New York, who also had a role in the design of the study, data collection and analysis, decision to publish, and preparation of the manuscript ([http://www.smafoundation.org/](http://www.smafoundation.org/)). Additional support for the described project by grant numbers CTSA Award 1 NIH UL1-RR-024134 (The Children’s Hospital of Philadelphia), UL1 RR025758-01 & MO1-RR02172 Children’s Hospital Boston; NIH 1 UL1 RR024156 Columbia University SMA Clinical Research Center; UL1-RR025755 The Ohio State University; 1UL1-RR024979, 1KL2-RR024980 & 1TL1-RR024981 University of Iowa; UL1-RR025764 & C06-RR11234 University of Utah; UL1-RR 025005 The Johns Hopkins University; UL1-RR024992 Washington University; UL1 RR025780 The Children’s Hospital – Denver; all from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, and its contents are sol

FAQs

What was the main objective of the BforSMA biomarker study?

To identify novel candidate biomarkers linked to disease severity in SMA using unbiased proteomic, metabolomic, and transcriptomic approaches.

How were disease severity and biomarker associations evaluated?

Associations were evaluated against the Modified Hammersmith Functional Motor Scale (MHFMS) as the primary severity measure, along with secondary clinical measures.

Which biomarker types were found to correlate with disease severity?

A total of 200 candidate biomarkers correlated with MHFMS scores: 97 plasma proteins and 59 plasma metabolites (including amino acids, free fatty acids, lipids, and GC/MS metabolites) plus 44 urine metabolites; no transcript biomarkers correlated with MHFMS.

Sep 3, 2026

Upload by McQueen