NN101 SMA

Spinal Muscular Atrophy (SMA) Biomarkers in the Immediate Postnatal Period of Development

Spinal muscular atrophy (SMA) is a rare, inherited disease that results in loss of nerves in the spinal cord and weakness of the muscles connected with those nerves. The muscles most frequently affected are those of the neck and trunk that control posture, those of the legs and arms that control movement, and those in the area of the ribs that help breathing. People with SMA generally appear normal at birth; the symptoms develop as early as 3 months in the most severely affected, around 1 to 2 years of age in the moderately affected, and more rarely in late childhood or adult years in mildly affected individuals.

There is no known treatment for SMA; historically, nearly half of babies born with the most severe form of the disease have died before two years of age.  All people with SMA have a higher than normal risk for progressive disability.  The most severely affected are at risk for breathing complications and early death.

NN101, a biomarker-driven study, was the first funded NeuroNEXT project. The goal was to identify laboratory measures to improve SMA clinical trials. Enrollment began in November, 2012 and ended September, 2014. Enrollment of all healthy control infants was completed in less than one year; enrollment of infants with SMA also occurred ahead of schedule. Retention was excellent and we have learned essential clinical trial lessons from the Super Babies!

From this study, we learned how motor function changes in infants and how biomarkers relate to motor function. Specifically, we learned:

  • How relevant physiological and molecular biomarkers change with time
  • How biomarkers correlate with motor function
  • How biomarkers predict future clinical outcomes
  • Which tests are important and which are probably not
  • Lessons about how best to design SMA clinical trials so that current and future trials will have a higher chance of success

Data collected in this study is important because:

  • It will accelerate the discovery and approval of SMA therapies
  • It will improve design of future SMA clinical trials
  • It will improve the design of future neonatal and pediatric clinical studies
  • It will lead to specific questions about the biology of SMA, which will result in a better understanding of the disease and better treatments for all people with SMA

We are grateful to the parents and their infants for their participation in this study. We also acknowledge the hard work and dedication of the 15 NeuroNEXT site coordinators, PIs and physical therapists who served as enrolling sites for this study. NN101 originated from The Ohio State University Wexner Medical Center and Nationwide Children’s Hospital in Columbus, OH. It was sponsored by NINDS (U01 NS079163), CureSMA, The Muscular Dystrophy Associate, SMA Foundation, Families of SMA, and WryBaby.com. The Avery Elementary Parent-Teacher Organization of Hilliard, Ohio has contributed travel funding as well.

Protocol Principal Investigator: 
Contact Information: 

For additional information, please contact: Amy.Bartlett@osumc.edu or call 1-855-SMA-BIOM (1-855-762-2466).

Publications: 
  • Bartlett, Amy, Kolb, Stephen J., Kinglsey, Allison, Swoboda, Kathryn J., Reyna, Sandra P., Sakonju, Ai, Darras, Basil T., Shell, Richard, Kuntz, Nancy, Castro, Diana, Iannaccone, Susan T., Parsons, Julie, Connolly, Anne M., Chiriboga, Claudia A., McDonald, Craig, Burnett, Bryan W., Werner, Klaus, Thangarajh, Mathula, Shieh, Perry B., Finanger, Erika, Coffey, Christopher S., Yankey, Jon W., Cudkowicz, Merit E., McGovern, Michelle M., McNeil, Elizabeth D., Arnold, David W., Kissel, John T., The NeuroNEXT Clinical Trial Network and on behalf of the NN101 SMA Biomarker Investigators. Recruitment & Retention Program for the NeuroNEXT SMA Biomarker Study: Super Babies for SMA! Contemporary Clinical Trials CommunicationsSeptember 201811113-119.

  • Rutkove SB, Darras BT NeuroNEXT is at your service. Annals of Neurology2017 Dec.82(6)857-858.

  • Kolb SJ, Coffey CS, Yankey JW, Korsschell KP, Arnold WD, Rutkove SB, Swoboda KJ, Reyna SP, Sakonju A, Darras BT, Shell R, Kuntz N, Castro D, Parsons J, Connolly A, Chiriboga CA, McDonald C, Burnette B, Werner W, Thangarajh M, Shieh P, Finanger E, Cudkowicz M, McGovern MM, McNeil DE, Finkel R, Iannacone ST, Kaye E, Kingsley A, Renusch SR, McGovern VL, Wang X, Zaworski PG, Prior TW, Burghes A, Bartlett AHM, Kissel JT the NeuroNEXT Clinical Trial Network and on behalf of the NN101 SMA Biomarker Investigators. Natural History of Infantile-Onset Spinal Muscular Atrophy. Annals of Neurology2017 Dec.82(6)883-891.
    PubMed: PMC5776712

  • Kolb SJ, Coffey CS, Yankey JW, Krosschell K, Arnold WD, Rutkove SB, Swoboda KJ, Reyna SP, Sakonju A, Darras BT, Shell R, Kuntz N, Castro D, Iannaccone ST, Parsons J, Connolly AM, Chiriboga CA, McDonald C, Burnette WB, Werner K, Thangarajh M, Shieh PB, Finanger E, Cudkowicz ME, McGovern MM, McNeil DE, Finkel R, Kaye E, Kingsley A, Renusch SR, McGovern VL, Wang X, Zaworski PG, Prior TW, Burghes AH, Bartlett A, Kissel JT; NeuroNEXT Clinical Trial Network and on behalf of the NN101 SMA Biomarker Investigators. Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study. Annals of Clinical and Translational Neurology20163(2)132-45.
    PubMed: PMC4748311