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Ann Clin Transl Neurol. 2016 Jan 21;3(2):132-45. doi: 10.1002/acn3.283. eCollection 2016 Feb.

Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study.

Author information

1
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.
2
Department of Biostatistics Neuro NEXT Data Coordinating Center University of Iowa Iowa City Iowa.
3
Departments of Physical Therapy and Human Movement Sciences and Pediatrics Northwestern University Feinberg School of Medicine Chicago Illinois.
4
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.
5
Department of Neurology Beth Israel Deaconess Medical Center Boston Massachusetts.
6
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.
7
Departments of Neurology and Pediatrics University of Utah Salt Lake City Utah.
8
Department of Neurology Boston Children's Hospital Boston Massachusetts.
9
Nationwide Children's Hospital Columbus Ohio.
10
Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois.
11
UT Southwestern Medical Center Dallas Texas.
12
Children's Hospital Colorado, University of Colorado School of Medicine Aurora Colorado.
13
Washington University School of Medicine in St. Louis St. Louis Missouri.
14
Department of Neurology Columbia College of Physicians and Surgeons New York New York.
15
University of California - Davis Davis California.
16
Vanderbilt University Nashville Tennessee.
17
SUNY Upstate Medical Center Syracuse New York.
18
Children's National Medical Center Washington District of Columbia.
19
University of California - Los Angeles Los Angeles California.
20
Dorenbecher Children's Hospital Portland Oregon.
21
Department of Neurology Neuro NEXT Clinical Coordinating Center Massachusetts General Hospital Boston Massachusetts.
22
National Institute of Neurological Disorders and Stroke Bethesda Maryland.
23
Nemours Children's Hospital Orlando Florida.
24
Sarepta Therapeutics Cambridge Massachusetts.
25
Department of Neurology The Ohio State University Wexner Medical Center Columbus Ohio.
26
Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus Ohio.
27
Pharm Optima Portage Michigan.
28
Department of Molecular Pathology Ohio State Wexner Medical Center Columbus Ohio.

Abstract

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.

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