Spinal Muscular Atrophy (SMA) Biomarkers Study in the Immediate Postnatal Period of Development
NCT ID: NCT01736553
Last Updated: 2018-05-04
Study Results
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View full resultsBasic Information
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COMPLETED
53 participants
OBSERVATIONAL
2012-12-31
2015-09-30
Brief Summary
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Detailed Description
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Aim 2. To establish the validity of putative molecular SMA biomarkers in the immediate postnatal period. Survival Motor Neuron (SMN2) copy number is a valid, predictive molecular SMA biomarker; however, it is fixed, and therefore not useful as a biomarker of clinical progression or response to therapy. SMN messenger Ribonucleic acid (mRNA) ( and protein expression is variable in different cell types and, in mice, naturally decreases with age postnatally. In this study, SMN expression levels will be measured longitudinally in SMA patients and controls. Additional putative molecular SMA markers that have been identified to correlate with motor function will be determined in an effort to distinguish between predictive markers that change prior to development of weakness and those that change as a consequence of weakness.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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Infants with Spinal Muscular Atrophy
Infants diagnosed Spinal Muscular Atrophy
No interventions assigned to this group
Healthy controls
Healthy control infants
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
The infants with SMA must have already had a positive DNA test outside of the study to qualify for enrollment. An infant with SMA can have any number of SMN2 gene copies. Knowledge of the number of SMN2 gene copies prior to enrollment is not required.
Healthy control infants who meet the following criteria will be enrolled:
* Birth between 36 and 42 weeks inclusive of gestation
* Siblings of children with SMA must have had prior SMA genetic testing completed con-firming the infant is a healthy control
* Principal investigator feels the family/infant is able and willing to comply with study procedures
* Parent or guardian able to give informed consent
SMA infants who meet the following criteria will be enrolled:
* Birth between 36 and 42 weeks inclusive of gestation
* Positive SMN1 gene mutation/deletion
* Principal investigator feels the family/infant is able and willing to comply with study procedures
* Parent or guardian able to give informed consent
Exclusion Criteria
* Enrollment in an SMA therapeutic trial at the time of enrollment in the SMA biomarker study
* Have a systemic illness requiring ongoing treatment, such as pneumonia
* Clinically significant abnormal findings (as determined by the investigator) on the physical examination or medical history (including history of tracheostomy tubes and ventilator-dependency)
* Dependency upon non-invasive ventilatory support (ie: BiPAP) for more than 12 hours/day
6 Months
ALL
Yes
Sponsors
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National Institute of Neurological Disorders and Stroke (NINDS)
NIH
Cure SMA
OTHER
Massachusetts General Hospital
OTHER
University of Iowa
OTHER
Ohio State University
OTHER
Responsible Party
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Stephen J. Kolb
Prinicipal Investigator of NeuroNEXT
Principal Investigators
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Stephen J Kolb, MD PhD
Role: PRINCIPAL_INVESTIGATOR
Ohio State University
Locations
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University of California - Davis
Davis, California, United States
University of California - Los Angeles
Los Angeles, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Boston Children's Hospital
Boston, Massachusetts, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Washington University in St. Louis School of Medicine
St Louis, Missouri, United States
Columbia University Medical Center
New York, New York, United States
State University of New York Upstate Medical Center
Syracuse, New York, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Doernbecher Children's Hospital
Portland, Oregon, United States
Vanderbilt University
Nashville, Tennessee, United States
Children's Medical Center of Dallas
Dallas, Texas, United States
University of Utah Health Sciences Center
Salt Lake City, Utah, United States
Countries
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References
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Campbell SK, Swanlund A, Smith E, Liao PJ, Zawacki L. Validity of the TIMPSI for estimating concurrent performance on the test of infant motor performance. Pediatr Phys Ther. 2008 Spring;20(1):3-10. doi: 10.1097/PEP.0b013e31815f66a6.
Dominguez E, Marais T, Chatauret N, Benkhelifa-Ziyyat S, Duque S, Ravassard P, Carcenac R, Astord S, Pereira de Moura A, Voit T, Barkats M. Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice. Hum Mol Genet. 2011 Feb 15;20(4):681-93. doi: 10.1093/hmg/ddq514. Epub 2010 Nov 30.
Finkel RS, Hynan LS, Glanzman AM, Owens H, Nelson L, Cone SR, Campbell SK, Iannaccone ST; AmSMART Group. The test of infant motor performance: reliability in spinal muscular atrophy type I. Pediatr Phys Ther. 2008 Fall;20(3):242-6. doi: 10.1097/PEP.0b013e318181ae96.
Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010 Mar;28(3):271-4. doi: 10.1038/nbt.1610. Epub 2010 Feb 28.
Hua Y, Sahashi K, Hung G, Rigo F, Passini MA, Bennett CF, Krainer AR. Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev. 2010 Aug 1;24(15):1634-44. doi: 10.1101/gad.1941310. Epub 2010 Jul 12.
Kolb SJ, Gubitz AK, Olszewski RF Jr, Ottinger E, Sumner CJ, Fischbeck KH, Dreyfuss G. A novel cell immunoassay to measure survival of motor neurons protein in blood cells. BMC Neurol. 2006 Feb 1;6:6. doi: 10.1186/1471-2377-6-6.
Kolb SJ, Kissel JT. Spinal muscular atrophy: a timely review. Arch Neurol. 2011 Aug;68(8):979-84. doi: 10.1001/archneurol.2011.74. Epub 2011 Apr 11.
Le TT, McGovern VL, Alwine IE, Wang X, Massoni-Laporte A, Rich MM, Burghes AH. Temporal requirement for high SMN expression in SMA mice. Hum Mol Genet. 2011 Sep 15;20(18):3578-91. doi: 10.1093/hmg/ddr275. Epub 2011 Jun 13.
Lutz CM, Kariya S, Patruni S, Osborne MA, Liu D, Henderson CE, Li DK, Pellizzoni L, Rojas J, Valenzuela DM, Murphy AJ, Winberg ML, Monani UR. Postsymptomatic restoration of SMN rescues the disease phenotype in a mouse model of severe spinal muscular atrophy. J Clin Invest. 2011 Aug;121(8):3029-41. doi: 10.1172/JCI57291. Epub 2011 Jul 25.
Morton JP, MacLaren DP, Cable NT, Bongers T, Griffiths RD, Campbell IT, Evans L, Kayani A, McArdle A, Drust B. Time course and differential responses of the major heat shock protein families in human skeletal muscle following acute nondamaging treadmill exercise. J Appl Physiol (1985). 2006 Jul;101(1):176-82. doi: 10.1152/japplphysiol.00046.2006. Epub 2006 Mar 24.
Narver HL, Kong L, Burnett BG, Choe DW, Bosch-Marce M, Taye AA, Eckhaus MA, Sumner CJ. Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition. Ann Neurol. 2008 Oct;64(4):465-70. doi: 10.1002/ana.21449.
Passini MA, Bu J, Richards AM, Kinnecom C, Sardi SP, Stanek LM, Hua Y, Rigo F, Matson J, Hung G, Kaye EM, Shihabuddin LS, Krainer AR, Bennett CF, Cheng SH. Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy. Sci Transl Med. 2011 Mar 2;3(72):72ra18. doi: 10.1126/scitranslmed.3001777.
Piper MC, Pinnell LE, Darrah J, Maguire T, Byrne PJ. Construction and validation of the Alberta Infant Motor Scale (AIMS). Can J Public Health. 1992 Jul-Aug;83 Suppl 2:S46-50.
Porensky PN, Mitrpant C, McGovern VL, Bevan AK, Foust KD, Kaspar BK, Wilton SD, Burghes AH. A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse. Hum Mol Genet. 2012 Apr 1;21(7):1625-38. doi: 10.1093/hmg/ddr600. Epub 2011 Dec 20.
Rutkove SB, Shefner JM, Gregas M, Butler H, Caracciolo J, Lin C, Fogerson PM, Mongiovi P, Darras BT. Characterizing spinal muscular atrophy with electrical impedance myography. Muscle Nerve. 2010 Dec;42(6):915-21. doi: 10.1002/mus.21784.
Tiziano FD, Pinto AM, Fiori S, Lomastro R, Messina S, Bruno C, Pini A, Pane M, D'Amico A, Ghezzo A, Bertini E, Mercuri E, Neri G, Brahe C. SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR. Eur J Hum Genet. 2010 Jan;18(1):52-8. doi: 10.1038/ejhg.2009.116.
Valori CF, Ning K, Wyles M, Mead RJ, Grierson AJ, Shaw PJ, Azzouz M. Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy. Sci Transl Med. 2010 Jun 9;2(35):35ra42. doi: 10.1126/scitranslmed.3000830.
Other Identifiers
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NN101
Identifier Type: -
Identifier Source: org_study_id
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