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Published on: November 3, 2016
Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study
Stephen J Kolb1, Christopher S Coffey2, Jon W Yankey2
1Department of Neurology The Ohio State University Wexner Medical Center Columbus Ohio; Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus Ohio.
Insights
This study identified key biomarkers for assessing infants with spinal muscular atrophy (SMA). Biomarkers like ulnar compound muscle action potential amplitude (CMAP) and survival motor neuron (SMN) mRNA levels effectively distinguished SMA infants from healthy controls.
Area of Science:
- Neurology
- Biomarker Discovery
- Pediatric Research
Background:
- Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder affecting infants.
- Early diagnosis and assessment are crucial for timely intervention and management of SMA.
- Identifying reliable biomarkers aids in understanding disease progression and treatment efficacy.
Purpose of the Study:
- To prospectively evaluate promising biomarkers for assessing infants diagnosed with SMA.
- To compare motor function and various biomarker levels between SMA infants and healthy controls.
- To determine the utility of electrophysiological, molecular, and protein biomarkers in distinguishing SMA from typical development.
Main Methods:
- A prospective, multi-center natural history study enrolled SMA and healthy control infants under 6 months.
- Motor function was assessed using standardized scales (TIMPSI, CHOP-INTEND).
- Electrophysiological (ulnar CMAP, EIM), molecular (SMN mRNA), and protein biomarkers were measured at baseline.
Main Results:
- Significant differences in motor function (TIMPSI, CHOP-INTEND) were observed between SMA and control infants.
- Reduced ulnar CMAP and altered EIM high-frequency reactance slope were found in SMA infants.
- Lower SMN mRNA levels and distinct serum protein profiles were identified in SMA infants compared to controls.
Conclusions:
- By the time of enrollment, SMA infants exhibited impaired motor function and distinct biomarker profiles.
- Ulnar CMAP, EIM, SMN mRNA levels, and serum protein analytes serve as effective discriminators between SMA and control infants.
- These validated biomarkers hold promise for future assessments in infant SMA studies.
Objective:
This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).
Methods:
This prospective, multi-center natural history study targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales and putative electrophysiological, protein and molecular biomarkers were assessed at baseline and subsequent visits.
Results:
Enrollment began November, 2012 and ended September, 2014 with 26 SMA infants and 27 healthy infants enrolled. Baseline demographic characteristics of the SMA and control infant cohorts aligned well. Motor function as assessed by the Test for Infant Motor Performance Items (TIMPSI) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) revealed significant differences between the SMA and control infants at baseline. Ulnar compound muscle action potential amplitude (CMAP) in SMA infants (1.4 ± 2.2 mV) was significantly reduced compared to controls (5.5 ± 2.0 mV). Electrical impedance myography (EIM) high-frequency reactance slope (Ohms/MHz) was significantly higher in SMA infants than controls SMA infants had lower survival motor neuron (SMN) mRNA levels in blood than controls, and several serum protein analytes were altered between cohorts.
Interpretation:
By the time infants were recruited and presented for the baseline visit, SMA infants had reduced motor function compared to controls. Ulnar CMAP, EIM, blood SMN mRNA levels, and serum protein analytes were able to distinguish between cohorts at the enrollment visit.
