Molecular Biomarkers for Spinal Muscular Atrophy

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: 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 mild/moderate SMA patients and healthy controls. Plasma phosphorylated neurofilament heavy chain (pNF-H) positively correlated 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 SMA patients 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.