Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2024 Dec;70(6):1247-1256.
doi: 10.1002/mus.28267. Epub 2024 Oct 6.

Outcomes of early-treated infants with spinal muscular atrophy: A multicenter, retrospective cohort study

Natalie L Goedeker  1 , Amanda Rogers  2 , Mark Fisher  3 , Kapil Arya  4 , John F Brandsema  5 , Hiba Farah  5 , Michelle A Farrar  6 , Marcia V Felker  7 , Melissa Gibbons  8 , Omer Abdul Hamid  9 , Matthew Harmelink  10 , Karen Herbert  6 , Elizabeth Kichula  5 , Kiana King  11 , Arpita Lakhotia  2 , Bo Hoon Lee  12 , Nancy L Kuntz  11 , Julie Parsons  8 , Rebecca Rehborg  10 , Aravindhan Veerapaniyan  4 , Craig M Zaidman  1
Affiliations
Multicenter Study

Outcomes of early-treated infants with spinal muscular atrophy: A multicenter, retrospective cohort study

Natalie L Goedeker et al. Muscle Nerve. 2024 Dec.

Abstract

Introduction/aims: While prompt identification and treatment of infants with spinal muscular atrophy (SMA) can ameliorate outcomes, variability persists. This study assessed management and outcomes of early-treated infants with SMA.

Methods: We analyzed retrospective data at 12 centers on infants with SMA treated at age ≤6 weeks from August 2018 to December 2023.

Results: Sixty-six patients, 35 with two SMN2 copies and 31 with ≥3 SMN2 copies, were included. Twenty-five (38%, 22 with two SMN2 copies), had SMA findings before initial treatment which was onasemnogene abeparvovec in 47 (71%) and nusinersen in 19 (29%). Thirty-two received sequential or combination treatments, including 16 adding nusinersen or risdiplam due to SMA findings following onasemnogene abeparvovec. All sat independently. Compared to children with ≥3 SMN2 copies, those with two SMN2 copies were less likely to walk (23/34 [68%] vs. 31/31 [100%], p < .001) and less likely to walk on time (9/34 [26%] vs. 29/31 [94%], p < .001); one non-ambulatory child was <18 months old and was excluded from this analysis. No patients required permanent ventilation or exclusively enteral nutrition; six required nocturnal non-invasive ventilation and four utilized supplemental enteral nutrition, all with two SMN2 copies.

Discussion: Early treatment of infants with SMA can improve outcomes as indicated by our cohort, all of whom sat independently and are without permanent ventilation. However, our study demonstrates ongoing disability in most children with two SMN2 copies despite early monotherapy and emphasizes the need for additional research, including earlier monotherapy, initial combination therapy, prenatal treatment, and non-SMN modifying treatments.

Keywords: CHOP INTEND; newborn screening; nusinersen; onasemnogene abeparvovec; spinal muscular atrophy.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. CHOP INTEND scores over time
CHOP INTEND scores over time through age 24 months. One patient with two SMN2 copies who was not yet walking but still within developmental window at last follow-up is not depicted. Solid lines represent patients without symptoms of SMA at initial treatment. Dashed lines represent patients with SMA symptoms at initial treatment. Abbreviations: SMN, survival motor neuron; CHOP INTEND, Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders; SMA, spinal muscular atrophy
Figure 1.
Figure 1.. CHOP INTEND scores over time
CHOP INTEND scores over time through age 24 months. One patient with two SMN2 copies who was not yet walking but still within developmental window at last follow-up is not depicted. Solid lines represent patients without symptoms of SMA at initial treatment. Dashed lines represent patients with SMA symptoms at initial treatment. Abbreviations: SMN, survival motor neuron; CHOP INTEND, Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders; SMA, spinal muscular atrophy
Figure 2:
Figure 2:. Acquisition of developmental milestones
Achievement of independent sitting and walking by SMN2 copy number. The age at first achievement of sitting and walking is shown in children with two SMN2 copies and >=three SMN2 copies. Gray shading indicates the WHO motor milestone for first through 99th percentiles of age at achievement for healthy, typically developing children: sitting without support (3.8 and 9.2 months, respectively) and walking alone (8.2 and 17.6 months, respectively)24. Abbreviations: SMN, survival motor neuron; WHO, World Health Organization
Figure 3.
Figure 3.. CHOP INTEND scores over time in combination therapy treated patients
CHOP INTEND scores over time in children receiving combination therapy. The dotted vertical line represents the time point of initiation of combination therapy, with CHOP INTEND scores on monotherapy to the left of the line and scores after combination therapy to the right of the line. Each line/shade represents an individual patient. Abbreviations: CHOP INTEND, Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders
See this image and copyright information in PMC

References

    1. Burghes AH, Beattie CE. Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick? Nat Rev Neurosci. Aug 2009;10(8):597–609. doi: 10.1038/nrn2670 - DOI - PMC - PubMed
    1. Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. Jan 13 1995;80(1):155–65. doi: 10.1016/0092-8674(95)90460-3 - DOI - PubMed
    1. Lefebvre S, Burlet P, Liu Q, et al. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet. Jul 1997;16(3):265–9. doi: 10.1038/ng0797-265 - DOI - PubMed
    1. Calucho M, Bernal S, Alías L, et al. Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases. Neuromuscul Disord. Mar 2018;28(3):208–215. doi: 10.1016/j.nmd.2018.01.003 - DOI - PubMed
    1. Feldkötter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet. Feb 2002;70(2):358–68. doi: 10.1086/338627 - DOI - PMC - PubMed

Publication types