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Review
. 2021 Aug;11(4):e524-e536.
doi: 10.1212/CPJ.0000000000000872.

Molecular Biomarkers for Spinal Muscular Atrophy: A Systematic Review

Angela Navarrete-Opazo  1 , Sheldon Garrison  1 , Mindy Waite  1
Affiliations
Review

Molecular Biomarkers for Spinal Muscular Atrophy: A Systematic Review

Angela Navarrete-Opazo et al. Neurol Clin Pract. 2021 Aug.

Abstract

Background: There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose of this review is to evaluate the clinical utility of blood-based biomarkers in patients with SMA.

Methods: A systematic review of MEDLINE, DARE, PEDro, PsycINFO, Cochrane Database, LILACS, OTSeeker, SpeechBITE, CINAHL, Scopus, Science Direct, clinicaltrial.gov, OpenGrey, and Google Scholar was performed with the last search data of June 30, 2019.

Results: Survival motor neuron (SMN)-related biomarkers showed an important interpatient and cell variability with a wide overlap between SMA phenotypes and healthy controls. Several plasma protein analytes correlated with motor scores; however, validation studies are needed to rule out false positives. DNA methylation analysis distinguished between patients with mild/moderate SMA and healthy controls. Plasma phosphorylated neurofilament heavy chain (pNF-H) levels increased with disease severity and declined considerably after nusinersen treatment.

Conclusion: There is no sufficient evidence to support the clinical utility of SMN-related biomarkers to predict disease severity in SMA. pNF-H appears to be a promising biomarker of disease activity and treatment effect in SMA. Further studies should include longitudinal assessments of patients with SMA across functional groups and comparisons with age-matched healthy controls to evaluate the stability of putative biomarkers over time and in response to SMA therapeutics. PROSPERO registration: CRD42019139050.

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Figures

Figure 1
Figure 1. Evaluation of Study Quality Using QUADAS Risk of Bias
Risk of bias was categorized as low (gray) or high (white). QUADAS-2 = Quality Assessment of Diagnostic Accuracy Study.
Figure 2
Figure 2. Flowchart Showing Preferred Reporting Items for Systematic Reviews and Meta-analyses Study Selection Process
See this image and copyright information in PMC

References

    1. Schmalbruch H, Haase G. Spinal muscular atrophy: present state. Brain Pathol 2001;11:231–247. - PMC - PubMed
    1. Lefebvre S, Bürglen L, Reboullet S, et al. . Identification and characterization of a spinal muscular atrophy-determining gene. Cell 1995;80:155–165. - PubMed
    1. Brzustowicz LM, Lehner T, Castilla LH, et al. . Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3. Nature 1990;344:540–541. - PubMed
    1. Monani UR, De Vivo DC. Neurodegeneration in spinal muscular atrophy: from disease phenotype and animal models to therapeutic strategies and beyond. Future Neurol 2014;9:49–65. - PMC - PubMed
    1. Darras BT, Jones HR, Ryan MM, De Vivo DC. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's Approach. 2015: Available at: www.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C20130000771. Accessed October 15, 2019.