Journal article
Natural history of infantile-onset spinal muscular atrophy
Annals of neurology, Vol.82(6), pp.883-891
12/2017
DOI: 10.1002/ana.25101
PMCID: PMC5776712
PMID: 29149772
Abstract
Infantile-onset spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, typically resulting in death preceding age 2. Clinical trials in this population require an understanding of disease progression and identification of meaningful biomarkers to hasten therapeutic development and predict outcomes.
A longitudinal, multicenter, prospective natural history study enrolled 26 SMA infants and 27 control infants aged <6 months. Recruitment occurred at 14 centers over 21 months within the NINDS-sponsored NeuroNEXT (National Network for Excellence in Neuroscience Clinical Trials) Network. Infant motor function scales (Test of Infant Motor Performance Screening Items [TIMPSI], The Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders, and Alberta Infant Motor Score) and putative physiological and molecular biomarkers were assessed preceding age 6 months and at 6, 9, 12, 18, and 24 months with progression, correlations between motor function and biomarkers, and hazard ratios analyzed.
Motor function scores (MFS) and compound muscle action potential (CMAP) decreased rapidly in SMA infants, whereas MFS in all healthy infants rapidly increased. Correlations were identified between TIMPSI and CMAP in SMA infants. TIMPSI at first study visit was associated with risk of combined endpoint of death or permanent invasive ventilation in SMA infants. Post-hoc analysis of survival to combined endpoint in SMA infants with 2 copies of SMN2 indicated a median age of 8 months at death (95% confidence interval, 6, 17).
These data of SMA and control outcome measures delineates meaningful change in clinical trials in infantile-onset SMA. The power and utility of NeuroNEXT to provide "real-world," prospective natural history data sets to accelerate public and private drug development programs for rare disease is demonstrated. Ann Neurol 2017;82:883-891.
Details
- Title: Subtitle
- Natural history of infantile-onset spinal muscular atrophy
- Creators
- Stephen J Kolb - Department of Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OHChristopher S Coffey - Department of Biostatistics, NeuroNEXT Data Coordinating Center, University of Iowa, Iowa City, IAJon W Yankey - Department of Biostatistics, NeuroNEXT Data Coordinating Center, University of Iowa, Iowa City, IAKristin Krosschell - Departments of Physical Therapy and Human Movement Sciences and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, ILW David Arnold - Department of Physical Medicine and Rehabilitation, The Ohio State University Wexner Medical Center, Columbus, OHSeward B Rutkove - Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MAKathryn J Swoboda - Department of Neurology, Boston Children's Hospital, Boston, MASandra P Reyna - Biogen, Boston, MAAi Sakonju - SUNY Upstate Medical Center, Syracuse, NYBasil T Darras - Department of Neurology, Boston Children's Hospital, Boston, MARichard Shell - Nationwide Children's Hospital, Columbus, OHNancy Kuntz - Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, ILDiana Castro - UT Southwestern Medical Center, Dallas, TXJulie Parsons - Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, COAnne M Connolly - Washington University School of Medicine in St. Louis, St. Louis, MOClaudia A Chiriboga - Department of Neurology, Columbia College of Physicians and Surgeons, New York, NYCraig McDonald - University of California-Davis, Davis, CAW Bryan Burnette - Vanderbilt University, Nashville, TNKlaus Werner - SUNY Upstate Medical Center, Syracuse, NYMathula Thangarajh - Children's National Medical Center, Washington, DCPerry B Shieh - University of California-Los Angeles, Los Angeles, CAErika Finanger - Dorenbecher Children's Hospital, Portland, ORMerit E Cudkowicz - Department of Neurology, NeuroNEXT Clinical Coordinating Center, Massachusetts General Hospital, Boston, MAMichelle M McGovern - Department of Neurology, NeuroNEXT Clinical Coordinating Center, Massachusetts General Hospital, Boston, MAD Elizabeth McNeil - National Institute of Neurological Disorders and Stroke, Bethesda, MDRichard Finkel - Nemours Children's Hospital, Orlando, FLSusan T Iannaccone - UT Southwestern Medical Center, Dallas, TXEdward Kaye - Sarepta Therapeutics, Cambridge, MAAllison Kingsley - Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OHSamantha R Renusch - Department of Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OHVicki L McGovern - Department of Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OHXueqian Wang - Department of Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OHPhillip G Zaworski - PharmOptima, Portage, MIThomas W Prior - Department of Molecular Pathology, Ohio State Wexner Medical Center, Columbus, OHArthur H M Burghes - Department of Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OHAmy Bartlett - Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OHJohn T Kissel - Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OHNeuroNEXT Clinical Trial Network on behalf of the NN101 SMA Biomarker Investigators
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.82(6), pp.883-891
- DOI
- 10.1002/ana.25101
- PMID
- 29149772
- PMCID
- PMC5776712
- NLM abbreviation
- Ann Neurol
- ISSN
- 1531-8249
- eISSN
- 1531-8249
- Publisher
- United States
- Grant note
- K12 HD001097 / NICHD NIH HHS U01 NS077352 / NINDS NIH HHS U24 NS107128 / NINDS NIH HHS U01 NS077179 / NINDS NIH HHS U01 NS079163 / NINDS NIH HHS
- Language
- English
- Date published
- 12/2017
- Academic Unit
- Biostatistics
- Record Identifier
- 9983997320002771
Metrics
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