Journal article
Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study
Annals of clinical and translational neurology, Vol.3(2), pp.132-145
02/2016
DOI: 10.1002/acn3.283
PMCID: PMC4748311
PMID: 26900585
Abstract
This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).
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.
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.
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.
Details
- Title: Subtitle
- Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study
- Creators
- Stephen J Kolb - Department of Neurology The Ohio State University Wexner Medical Center Columbus Ohio; Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus OhioChristopher S Coffey - Department of Biostatistics Neuro NEXT Data Coordinating Center University of Iowa Iowa City IowaJon W Yankey - Department of Biostatistics Neuro NEXT Data Coordinating Center University of Iowa Iowa City IowaKristin Krosschell - Departments of Physical Therapy and Human Movement Sciences and Pediatrics Northwestern University Feinberg School of Medicine Chicago IllinoisW David Arnold - Department of Neurology The Ohio State University Wexner Medical Center Columbus Ohio; Department of Physical Medicine and Rehabilitation The Ohio State University Wexner Medical Center Columbus OhioSeward B Rutkove - Department of Neurology Beth Israel Deaconess Medical Center Boston MassachusettsKathryn J Swoboda - Departments of Neurology and Pediatrics University of Utah Salt Lake City Utah; Department of Neurology Neuro NEXT Clinical Coordinating Center Massachusetts General Hospital Boston MassachusettsSandra P Reyna - Departments of Neurology and Pediatrics University of Utah Salt Lake City Utah; Department of Neurology Neuro NEXT Clinical Coordinating Center Massachusetts General Hospital Boston MassachusettsAi Sakonju - Departments of Neurology and Pediatrics University of Utah Salt Lake City UtahBasil T Darras - Department of Neurology Boston Children's Hospital Boston MassachusettsRichard Shell - Nationwide Children's Hospital Columbus OhioNancy Kuntz - Ann & Robert H. Lurie Children's Hospital of Chicago Chicago IllinoisDiana Castro - UT Southwestern Medical Center Dallas TexasSusan T Iannaccone - UT Southwestern Medical Center Dallas TexasJulie Parsons - Children's Hospital Colorado, University of Colorado School of Medicine Aurora ColoradoAnne M Connolly - Washington University School of Medicine in St. Louis St. Louis MissouriClaudia A Chiriboga - Department of Neurology Columbia College of Physicians and Surgeons New York New YorkCraig McDonald - University of California - Davis Davis CaliforniaW Bryan Burnette - Vanderbilt University Nashville TennesseeKlaus Werner - SUNY Upstate Medical Center Syracuse New YorkMathula Thangarajh - Children's National Medical Center Washington District of ColumbiaPerry B Shieh - University of California - Los Angeles Los Angeles CaliforniaErika Finanger - Dorenbecher Children's Hospital Portland OregonMerit E Cudkowicz - Department of Neurology Neuro NEXT Clinical Coordinating Center Massachusetts General Hospital Boston MassachusettsMichelle M McGovern - Department of Neurology Neuro NEXT Clinical Coordinating Center Massachusetts General Hospital Boston MassachusettsD Elizabeth McNeil - National Institute of Neurological Disorders and Stroke Bethesda MarylandRichard Finkel - Nemours Children's Hospital Orlando FloridaEdward Kaye - Sarepta Therapeutics Cambridge MassachusettsAllison Kingsley - Department of Neurology The Ohio State University Wexner Medical Center Columbus OhioSamantha R Renusch - Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus OhioVicki L McGovern - Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus OhioXueqian Wang - Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus OhioPhillip G Zaworski - Pharm Optima Portage MichiganThomas W Prior - Department of Molecular Pathology Ohio State Wexner Medical Center Columbus OhioArthur H M Burghes - Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus OhioAmy Bartlett - Department of Neurology The Ohio State University Wexner Medical Center Columbus OhioJohn T Kissel - Department of Neurology The Ohio State University Wexner Medical Center Columbus OhioNeuroNEXT Clinical Trial Network and on behalf of the NN101 SMA Biomarker Investigators
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.3(2), pp.132-145
- DOI
- 10.1002/acn3.283
- PMID
- 26900585
- PMCID
- PMC4748311
- NLM abbreviation
- Ann Clin Transl Neurol
- ISSN
- 2328-9503
- eISSN
- 2328-9503
- Publisher
- United States
- Grant note
- K12 HD001097 / NICHD NIH HHS U54 HD087011 / NICHD NIH HHS U10 NS077269 / NINDS NIH HHS U01 NS077352 / NINDS NIH HHS U10 NS077260 / NINDS NIH HHS U01 NS077179 / NINDS NIH HHS U10 NS077382 / NINDS NIH HHS U01 NS079163 / NINDS NIH HHS UL1 TR000445 / NCATS NIH HHS U10 NS077420 / NINDS NIH HHS U10 NS077267 / NINDS NIH HHS K08 NS067282 / NINDS NIH HHS
- Language
- English
- Date published
- 02/2016
- Academic Unit
- Biostatistics
- Record Identifier
- 9983997308502771
Metrics
31 Record Views