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.
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.
Authors: Aga Lewelt; Kristin J Krosschell; Charles Scott; Ai Sakonju; John T Kissel; Thomas O Crawford; Gyula Acsadi; Guy D'anjou; Bakri Elsheikh; Sandra P Reyna; Mary K Schroth; Jo Anne Maczulski; Gregory J Stoddard; Elie Elovic; Kathryn J Swoboda Journal: Muscle Nerve Date: 2010-11 Impact factor: 3.217
Authors: Galina Y Zheleznyakova; Sarah Voisin; Anton V Kiselev; Markus Sällman Almén; Miguel J Xavier; Marianna A Maretina; Lyudmila I Tishchenko; Robert Fredriksson; Vladislav S Baranov; Helgi B Schiöth Journal: Eur J Hum Genet Date: 2013-01-09 Impact factor: 4.246
Authors: Richard S Finkel; Eugenio Mercuri; Basil T Darras; Anne M Connolly; Nancy L Kuntz; Janbernd Kirschner; Claudia A Chiriboga; Kayoko Saito; Laurent Servais; Eduardo Tizzano; Haluk Topaloglu; Már Tulinius; Jacqueline Montes; Allan M Glanzman; Kathie Bishop; Z John Zhong; Sarah Gheuens; C Frank Bennett; Eugene Schneider; Wildon Farwell; Darryl C De Vivo Journal: N Engl J Med Date: 2017-11-02 Impact factor: 91.245
Authors: Michael Khalil; Charlotte E Teunissen; Markus Otto; Fredrik Piehl; Maria Pia Sormani; Thomas Gattringer; Christian Barro; Ludwig Kappos; Manuel Comabella; Franz Fazekas; Axel Petzold; Kaj Blennow; Henrik Zetterberg; Jens Kuhle Journal: Nat Rev Neurol Date: 2018-10 Impact factor: 42.937
Authors: Richard S Finkel; Thomas O Crawford; Kathryn J Swoboda; Petra Kaufmann; Peter Juhasz; Xiaohong Li; Yu Guo; Rebecca H Li; Felicia Trachtenberg; Suzanne J Forrest; Dione T Kobayashi; Karen S Chen; Cynthia L Joyce; Thomas Plasterer Journal: PLoS One Date: 2012-04-27 Impact factor: 3.240
Authors: Dione T Kobayashi; Rory J Olson; Laurel Sly; Chad J Swanson; Brett Chung; Nikolai Naryshkin; Jana Narasimhan; Anuradha Bhattacharyya; Michael Mullenix; Karen S Chen Journal: PLoS One Date: 2011-08-31 Impact factor: 3.240