Natural history of infantile-onset spinal muscular atrophy

被引：308

作者：

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

Coffey, Christopher S. ^{[3
]}

Yankey, Jon W. ^{[3
]}

Krosschell, Kristin ^{[4
,5
]}

Arnold, W. David ^{[1
,6
]}

Rutkove, Seward B. ^{[7
]}

Swoboda, Kathryn J. ^{[8
,9
,10
]}

Reyna, Sandra P. ^{[8
,9
,11
]}

Sakonju, Ai ^{[8
,9
,20
]}

Darras, Basil T. ^{[10
]}

Shell, Richard ^{[12
]}

Kuntz, Nancy ^{[13
]}

Castro, Diana ^{[14
]}

Parsons, Julie ^{[15
]}

Connolly, Anne M. ^{[16
]}

Chiriboga, Claudia A. ^{[17
]}

McDonald, Craig ^{[18
]}

Burnette, W. Bryan ^{[19
]}

Werner, Klaus ^{[20
]}

Thangarajh, Mathula ^{[21
]}

Shieh, Perry B. ^{[22
]}

Finanger, Erika ^{[23
]}

Cudkowicz, Merit E. ^{[24
]}

McGovern, Michelle M. ^{[24
]}

McNeil, D. Elizabeth ^{[11
,25
]}

Finkel, Richard ^{[26
]}

Iannaccone, Susan T. ^{[14
]}

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, Wexner Med Ctr, Dept Neurol, Rightmire Hall,Room 226A,1060 Carmack Rd, Columbus, OH 43210 USA

[2] Ohio State Univ, Wexner Med Ctr, Dept Biol Chem & Pharmacol, Rightmire Hall,Room 226A,1060 Carmack Rd, 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 & Human Movement Sci, Chicago, IL 60611 USA

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

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

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

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

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

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

[11] Biogen, Boston, MA USA

[12] Nationwide Childrens Hosp, Columbus, OH USA

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

[14] UT Southwestern Med Ctr, Dallas, TX USA

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

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

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

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

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

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

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

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

[23] Dorenbecher Childrens Hosp, Portland, OR USA

[24] Massachusetts Gen Hosp, Dept Neurol, NeuroNEXT Clin Coordinating Ctr, Boston, MA 02114 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 NEUROLOGY | 2017年 / 82卷 / 06期

关键词：

SMN2 COPY NUMBER; SINGLE NUCLEOTIDE; GENE; SEVERITY; PROTEIN; SMA; CHILDREN; MOUSE; MODEL;

D O I：

10.1002/ana.25101

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

ObjectiveInfantile-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. MethodsA 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. ResultsMotor 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). InterpretationThese 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

引用

页码：883 / 891

页数：9

共 43 条

[1]

NeuroNEXT: accelerating drug development in neurology [J].

不详 .

LANCET NEUROLOGY, 2012, 11 (02) :119-119

[2]

The neuromuscular impact of symptomatic SMN restoration in a mouse model of spinal muscular atrophy [J].

Arnold, W. ;

McGovern, Vicki L. ;

Sanchez, Benjamin ;

Li, Jia ;

Corlett, Kaitlyn M. ;

Kolb, Stephen J. ;

Rutkove, Seward B. ;

Burghes, Arthur H. .

NEUROBIOLOGY OF DISEASE, 2016, 87 :116-123

[3]

Spinal Muscular Atrophy: Development and Implementation of Potential Treatments [J].

Arnold, W. David ;

Burghes, Arthur H. M. .

ANNALS OF NEUROLOGY, 2013, 74 (03) :348-362

[4]

Arnold WD, 2016, SMA BIOMARKERS

[5]

The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor [J].

Bernal, S. ;

Alias, L. ;

Barcelo, M. J. ;

Also-Rallo, E. ;

Martinez-Hernandez, R. ;

Gamez, J. ;

Guillen-Navarro, E. ;

Rosell, J. ;

Hernando, I. ;

Rodriguez-Alvarez, F. J. ;

Borrego, S. ;

Millan, J. M. ;

Hernandez-Chico, C. ;

Baiget, M. ;

Fuentes-Prior, P. ;

Tizzano, E. F. .

JOURNAL OF MEDICAL GENETICS, 2010, 47 (09) :640-642

[6]

Blanchard Y, 2004, Pediatr Phys Ther, V16, P13, DOI 10.1097/01.PEP.0000113272.34023.56

[7]

Regulation of SMN Protein Stability [J].

Burnett, Barrington G. ;

Munoz, Eric ;

Tandon, Animesh ;

Kwon, Deborah Y. ;

Sumner, Charlotte J. ;

Fischbeck, Kenneth H. .

MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (05) :1107-1115

[8]

Results from a phase 1 study of nusinersen (ISIS-SMNRx) in children with spinal muscular atrophy [J].

Chiriboga, Claudia A. ;

Swoboda, Kathryn J. ;

Darras, Basil T. ;

Iannaccone, Susan T. ;

Montes, Jacqueline ;

De Vivo, Darryl C. ;

Norris, Daniel A. ;

Bennett, C. Frank ;

Bishop, Kathie M. .

NEUROLOGY, 2016, 86 (10) :890-897

[9]

The survival motor neuron protein in spinal muscular atrophy [J].

Coovert, DD ;

Le, TT ;

McAndrew, PE ;

Strasswimmer, J ;

Crawford, TO ;

Mendell, JR ;

Coulson, SE ;

Androphy, EJ ;

Prior, TW ;

Burghes, AHM .

HUMAN MOLECULAR GENETICS, 1997, 6 (08) :1205-1214

[10]

Developmental milestones in type I spinal muscular atrophy [J].

De Sanctis, Roberto ;

Coratti, Giorgia ;

Pasternak, Amy ;

Montes, Jacqueline ;

Pane, Marika ;

Mazzone, Elena S. ;

Young, Sally Dunaway ;

Salazar, Rachel ;

Quigley, Janet ;

Pera, Maria C. ;

Antonaci, Laura ;

Lapenta, Leonardo ;

Glanzman, Allan M. ;

Tiziano, Danilo ;

Muntoni, Francesco ;

Darras, Basil T. ;

De Vivo, Darryl C. ;

Finkel, Richard ;

Mercuri, Eugenio .

NEUROMUSCULAR DISORDERS, 2016, 26 (11) :754-759

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