title: Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study.
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.
authors.affiliation: 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 Ohio.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kolb
authors.affiliation: Department of Biostatistics Neuro NEXT Data Coordinating Center University of Iowa Iowa City Iowa.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Coffey
authors.affiliation: Department of Biostatistics Neuro NEXT Data Coordinating Center University of Iowa Iowa City Iowa.
authors.forename: Jon W
authors.initials: JW
authors.lastname: Yankey
authors.affiliation: Departments of Physical Therapy and Human Movement Sciences and Pediatrics Northwestern University Feinberg School of Medicine Chicago Illinois.
authors.forename: Kristin
authors.initials: K
authors.lastname: Krosschell
authors.affiliation: 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 Ohio.
authors.forename: W David
authors.identifier: 0000-0001-9889-7036
authors.initials: WD
authors.lastname: Arnold
authors.affiliation: Department of Neurology Beth Israel Deaconess Medical Center Boston Massachusetts.
authors.forename: Seward B
authors.initials: SB
authors.lastname: Rutkove
authors.affiliation: Departments of Neurology and Pediatrics University of Utah Salt Lake City Utah; Department of Neurology Neuro NEXT Clinical Coordinating Center Massachusetts General Hospital Boston Massachusetts.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Swoboda
authors.affiliation: Departments of Neurology and Pediatrics University of Utah Salt Lake City Utah; Department of Neurology Neuro NEXT Clinical Coordinating Center Massachusetts General Hospital Boston Massachusetts.
authors.forename: Sandra P
authors.initials: SP
authors.lastname: Reyna
authors.affiliation: Departments of Neurology and Pediatrics University of Utah Salt Lake City Utah.
authors.forename: Ai
authors.initials: A
authors.lastname: Sakonju
authors.affiliation: Department of Neurology Boston Children's Hospital Boston Massachusetts.
authors.forename: Basil T
authors.initials: BT
authors.lastname: Darras
authors.affiliation: Nationwide Children's Hospital Columbus Ohio.
authors.forename: Richard
authors.initials: R
authors.lastname: Shell
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois.
authors.forename: Nancy
authors.initials: N
authors.lastname: Kuntz
authors.affiliation: UT Southwestern Medical Center Dallas Texas.
authors.forename: Diana
authors.initials: D
authors.lastname: Castro
authors.affiliation: UT Southwestern Medical Center Dallas Texas.
authors.forename: Susan T
authors.initials: ST
authors.lastname: Iannaccone
authors.affiliation: Children's Hospital Colorado, University of Colorado School of Medicine Aurora Colorado.
authors.forename: Julie
authors.initials: J
authors.lastname: Parsons
authors.affiliation: Washington University School of Medicine in St. Louis St. Louis Missouri.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Connolly
authors.affiliation: Department of Neurology Columbia College of Physicians and Surgeons New York New York.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Chiriboga
authors.affiliation: University of California - Davis Davis California.
authors.forename: Craig
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Vanderbilt University Nashville Tennessee.
authors.forename: W Bryan
authors.initials: WB
authors.lastname: Burnette
authors.affiliation: SUNY Upstate Medical Center Syracuse New York.
authors.forename: Klaus
authors.initials: K
authors.lastname: Werner
authors.affiliation: Children's National Medical Center Washington District of Columbia.
authors.forename: Mathula
authors.initials: M
authors.lastname: Thangarajh
authors.affiliation: University of California - Los Angeles Los Angeles California.
authors.forename: Perry B
authors.initials: PB
authors.lastname: Shieh
authors.affiliation: Dorenbecher Children's Hospital Portland Oregon.
authors.forename: Erika
authors.initials: E
authors.lastname: Finanger
authors.affiliation: Department of Neurology Neuro NEXT Clinical Coordinating Center Massachusetts General Hospital Boston Massachusetts.
authors.forename: Merit E
authors.initials: ME
authors.lastname: Cudkowicz
authors.affiliation: Department of Neurology Neuro NEXT Clinical Coordinating Center Massachusetts General Hospital Boston Massachusetts.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: McGovern
authors.affiliation: National Institute of Neurological Disorders and Stroke Bethesda Maryland.
authors.forename: D Elizabeth
authors.initials: DE
authors.lastname: McNeil
authors.affiliation: Nemours Children's Hospital Orlando Florida.
authors.forename: Richard
authors.initials: R
authors.lastname: Finkel
authors.affiliation: Sarepta Therapeutics Cambridge Massachusetts.
authors.forename: Edward
authors.initials: E
authors.lastname: Kaye
authors.affiliation: Department of Neurology The Ohio State University Wexner Medical Center Columbus Ohio.
authors.forename: Allison
authors.initials: A
authors.lastname: Kingsley
authors.affiliation: Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus Ohio.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Renusch
authors.affiliation: Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus Ohio.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: McGovern
authors.affiliation: Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus Ohio.
authors.forename: Xueqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Pharm Optima Portage Michigan.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Zaworski
authors.affiliation: Department of Molecular Pathology Ohio State Wexner Medical Center Columbus Ohio.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Prior
authors.affiliation: Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus Ohio.
authors.forename: Arthur H M
authors.initials: AH
authors.lastname: Burghes
authors.affiliation: Department of Neurology The Ohio State University Wexner Medical Center Columbus Ohio.
authors.forename: Amy
authors.initials: A
authors.lastname: Bartlett
authors.affiliation: Department of Neurology The Ohio State University Wexner Medical Center Columbus Ohio.
authors.forename: John T
authors.initials: JT
authors.lastname: Kissel