Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study

被引：104

作者：

Kolb, Stephen J. ^{[1
,2
]}

Coffey, Christopher S. ^{[3
]}

Yankey, Jon W. ^{[3
]}

Krosschell, Kristin ^{[4
,5
,6
]}

Arnold, W. David ^{[1
,7
]}

Rutkove, Seward B. ^{[8
]}

Swoboda, Kathryn J. ^{[9
,10
,11
]}

Reyna, Sandra P. ^{[9
,10
,11
]}

Sakonju, Ai ^{[9
,10
]}

Darras, Basil T. ^{[12
]}

Shell, Richard ^{[13
]}

Kuntz, Nancy ^{[14
]}

Castro, Diana ^{[15
]}

Iannaccone, Susan T. ^{[15
]}

Parsons, Julie ^{[16
]}

Connolly, Anne M. ^{[17
]}

Chiriboga, Claudia A. ^{[18
]}

McDonald, Craig ^{[19
]}

Burnette, W. Bryan ^{[20
]}

Werner, Klaus ^{[21
]}

Thangarajh, Mathula ^{[22
]}

Shieh, Perry B. ^{[23
]}

Finanger, Erika ^{[24
]}

Cudkowicz, Merit E. ^{[11
]}

McGovern, Michelle M. ^{[11
]}

McNeil, D. Elizabeth ^{[25
]}

Finkel, Richard ^{[26
]}

Kaye, Edward ^{[27
]}

Kingsley, Allison ^{[1
]}

Renusch, Samantha R. ^{[2
]}

McGovern, Vicki L. ^{[2
]}

Wang, Xueqian ^{[2
]}

Zaworski, Phillip G. ^{[28
]}

Prior, Thomas W. ^{[29
]}

Burghes, Arthur H. M. ^{[2
]}

Bartlett, Amy ^{[1
]}

Kissel, John T. ^{[1
]}

机构：

[1] Ohio State Univ, Dept Neurol, Wexner Med Ctr, Hamilton Hall,Room 337B,1645 Neil Ave, Columbus, OH 43210 USA

[2] Ohio State Univ, Dept Biol Chem & Pharmacol, Wexner Med Ctr, Hamilton Hall,Room 337B,1645 Neil Ave, Columbus, OH 43210 USA

[3] Univ Iowa, Dept Biostat, NeuroNEXT Data Coordinating Ctr, Iowa City, IA USA

[4] Northwestern Univ, Feinberg Sch Med, Dept Phys Therapy, Chicago, IL 60611 USA

[5] Northwestern Univ, Dept Human Movement Sci, Feinberg Sch Med, Chicago, IL 60611 USA

[6] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA

[7] Ohio State Univ, Wexner Med Ctr, Dept Phys Med & Rehabil, Columbus, OH 43210 USA

[8] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA

[9] Univ Utah, Dept Neurol, Salt Lake City, UT USA

[10] Univ Utah, Dept Pediat, Salt Lake City, UT USA

[11] Massachusetts Gen Hosp, Dept Neurol, NeuroNEXT Clin Coordinating Ctr, Boston, MA 02114 USA

[12] Boston Childrens Hosp, Dept Neurol, Boston, MA USA

[13] Nationwide Childrens Hosp, Columbus, OH USA

[14] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA

[15] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[16] Univ Colorado, Sch Med, Childrens Hosp Colorado, Aurora, CO USA

[17] Washington Univ, Sch Med, St Louis, MO USA

[18] Columbia Coll Phys & Surg, Dept Neurol, New York, NY USA

[19] Univ Calif Davis, Davis, CA 95616 USA

[20] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA

[21] SUNY Upstate Med Ctr, Syracuse, NY USA

[22] Childrens Natl Med Ctr, Washington, DC 20010 USA

[23] Univ Calif Los Angeles, Los Angeles, CA USA

[24] Dorenbecher Childrens Hosp, Portland, OR USA

[25] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[26] Nemours Childrens Hosp, Orlando, FL USA

[27] Sarepta Therapeut, Cambridge, MA USA

[28] PharmOptima, Portage, MI USA

[29] Ohio State Wexner Med Ctr, Dept Mol Pathol, Columbus, OH USA

来源：

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY | 2016年 / 3卷 / 02期

关键词：

ELECTRICAL-IMPEDANCE MYOGRAPHY; SMN2 COPY NUMBER; NATURAL-HISTORY; SINGLE NUCLEOTIDE; CLINICAL-TRIALS; GENE SMN2; PROTEIN; SURVIVAL; SEVERITY; SMA;

D O I：

10.1002/acn3.283

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

ObjectiveThis study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA). MethodsThis 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. ResultsEnrollment 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. InterpretationBy 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.

引用

页码：132 / 145

页数：14

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