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. 2024 Sep 2:15:1382410.
doi: 10.3389/fneur.2024.1382410. eCollection 2024.

Association among biomarkers, phenotypes, and motor milestones in Chinese patients with 5q spinal muscular atrophy types 1-3

Shijia Ouyang #  1 , Xiaoyin Peng #  2 , Wenchen Huang  1 , Jinli Bai  1 , Hong Wang  1 , Yuwei Jin  1 , Hui Jiao  2 , Maoti Wei  3 , Xiushan Ge  2 , Fang Song  1 , Yujin Qu  1
Affiliations

Association among biomarkers, phenotypes, and motor milestones in Chinese patients with 5q spinal muscular atrophy types 1-3

Shijia Ouyang et al. Front Neurol. .

Erratum in

Abstract

Background: Biomarkers can be used to assess the severity of spinal muscular atrophy (5q SMA; SMA). Despite their potential, the relationship between biomarkers and clinical outcomes in SMA remains underexplored. This study aimed to assess the association among biomarkers, phenotypes, and motor milestones in Chinese patients diagnosed with SMA.

Methods: We collected retrospective clinical and follow-up data of disease-modifying therapy (DMT)-naïve patients with SMA at our center from 2019 to 2021. Four biomarkers were included: survival motor neuron 2 (SMN2) copies, neuronal apoptosis inhibitory protein (NAIP) copies, full-length SMN2 (fl-SMN2), and F-actin bundling protein plastin 3 (PLS3) transcript levels. Data were analyzed and stratified according to SMA subtype.

Results: Of the 123 patients, 30 were diagnosed with Type 1 (24.3%), 56 with Type 2 (45.5%), and 37 with Type 3 (30.1%). The mortality rate for Type 1 was 50%, with median survival times of 2 and 8 months for types 1a and 1b, respectively. All four biomarkers were correlated with disease severity. Notably, fl-SMN2 transcript levels increased with SMN2 copies and were higher in Type 2b than those in Type 2a (p = 0.028). Motor milestone deterioration was correlated with SMN2 copies, NAIP copies, and fl-SMN2 levels, while PLS3 levels were correlated with standing and walking function.

Discussion: Our findings suggest that SMN2 copies contribute to survival and that fl-SMN2 may serve as a valuable biomarker for phenotypic variability in SMA Type 2 subtypes. These insights can guide future research and clinical management of SMA.

Keywords: biomarkers; motor milestones; severity; spinal muscular atrophy; survival.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Composite endpoint survival curves of patients with SMA Type 1 and subtypes. (A) Composite endpoint survival curve of patients with SMA Type 1 disease using Kaplan–Meier analysis. (B) Composite endpoint survival curve of patients with SMA types 1a, 1b, and 1c using Kaplan–Meier analysis. SMA, spinal muscular atrophy; NAIP, neuronal apoptosis inhibitory protein.
Figure 2
Figure 2
Milestone acquisition and loss in patients with different SMA subtypes and curves of motor milestone deterioration. (A) Milestone acquisition and loss in patients with different SMA subtypes. The number indicates the age at milestone acquisition or loss, shown as the median (minimum–maximum). The percentage in the figure represents the proportion of milestone acquisition or loss cases within subtype groups. * Indicates that only one case showed milestone acquisition or loss. SMA, spinal muscular atrophy. (B) Curve of rolling deterioration in SMA subtypes 1c, 2a, and 2b using Kaplan–Meier analysis. (C) Curve of sitting deterioration in SMA subtypes 2a and 2b using Kaplan–Meier analysis. (D) Curve of walking deterioration in SMA subtypes 3a and 3b using Kaplan–Meier analysis.
Figure 3
Figure 3
Distribution of SMN2 and NAIP copy numbers and their impact on composite endpoint survival in patients with SMA types 1–3. (A) Distribution of SMN2 copy numbers in patients with SMA types 1–3. (B) Distribution of NAIP copy numbers in patients with SMA types 1–3. (C) Impact of SMN2 copy number on composite endpoint survival in patients with SMA types 1–3. (D) Impact of NAIP copy number on composite endpoint survival in patients with SMA types 1–3. SMA, spinal muscular atrophy; NAIP, neuronal apoptosis inhibitory protein.
Figure 4
Figure 4
Correlation of fl-SMN2 expression with phenotype severity and SMN2 copy number. (A) Correlation between fl-SMN2 expression and phenotype severity. (B) Correlation between fl-SMN2 expression and SMN2 copy number. (C) fl-SMN2 transcript levels in the composite endpoint and survival groups of patients with Type 1–3 SMA and (D) PLS3 transcript levels in the composite endpoint and survival groups of patients with Type 1–3 SMA.
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