TY - JOUR
T1 - Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study
AU - The NeuroNEXT Clinical Trial Network and on behalf of the NN101 SMA Biomarker Investigators
AU - Kolb, Stephen J.
AU - Coffey, Christopher S.
AU - Yankey, Jon W.
AU - Krosschell, Kristin
AU - Arnold, W. David
AU - Rutkove, Seward B.
AU - Swoboda, Kathryn J.
AU - Reyna, Sandra P.
AU - Sakonju, Ai
AU - Darras, Basil T.
AU - Shell, Richard
AU - Kuntz, Nancy
AU - Castro, Diana
AU - Iannaccone, Susan T.
AU - Parsons, Julie
AU - Connolly, Anne M.
AU - Chiriboga, Claudia A.
AU - Mcdonald, Craig
AU - Burnette, W. Bryan
AU - Werner, Klaus
AU - Thangarajh, Mathula
AU - Shieh, Perry B.
AU - Finanger, Erika
AU - Cudkowicz, Merit E.
AU - Mcgovern, Michelle M.
AU - Mcneil, D. Elizabeth
AU - Finkel, Richard
AU - Kaye, Edward
AU - Kingsley, Allison
AU - Renusch, Samantha R.
AU - Mcgovern, Vicki L.
AU - Wang, Xueqian
AU - Zaworski, Phillip G.
AU - Prior, Thomas W.
AU - Burghes, Arthur H.M.
AU - Bartlett, Amy
AU - Kissel, John T.
N1 - Publisher Copyright:
© 2016 American Neurological Association.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84962331895&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962331895&partnerID=8YFLogxK
U2 - 10.1002/acn3.283
DO - 10.1002/acn3.283
M3 - Article
C2 - 26900585
AN - SCOPUS:84962331895
SN - 2328-9503
VL - 3
SP - 132
EP - 145
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
IS - 2
ER -