{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:55:33Z","timestamp":1787068533937,"version":"build-2736575974"},"reference-count":108,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["IP-2019-04-3584"],"award-info":[{"award-number":["IP-2019-04-3584"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["BM99\/2020"],"award-info":[{"award-number":["BM99\/2020"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["2022_10106-22-3101"],"award-info":[{"award-number":["2022_10106-22-3101"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["GA KK01.1.1.01.0007"],"award-info":[{"award-number":["GA KK01.1.1.01.0007"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The University of Zagreb","award":["IP-2019-04-3584"],"award-info":[{"award-number":["IP-2019-04-3584"]}]},{"name":"The University of Zagreb","award":["BM99\/2020"],"award-info":[{"award-number":["BM99\/2020"]}]},{"name":"The University of Zagreb","award":["2022_10106-22-3101"],"award-info":[{"award-number":["2022_10106-22-3101"]}]},{"name":"The University of Zagreb","award":["GA KK01.1.1.01.0007"],"award-info":[{"award-number":["GA KK01.1.1.01.0007"]}]},{"name":"Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience CoRE-NEURO","award":["IP-2019-04-3584"],"award-info":[{"award-number":["IP-2019-04-3584"]}]},{"name":"Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience CoRE-NEURO","award":["BM99\/2020"],"award-info":[{"award-number":["BM99\/2020"]}]},{"name":"Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience CoRE-NEURO","award":["2022_10106-22-3101"],"award-info":[{"award-number":["2022_10106-22-3101"]}]},{"name":"Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience CoRE-NEURO","award":["GA KK01.1.1.01.0007"],"award-info":[{"award-number":["GA KK01.1.1.01.0007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a progressive degenerative illness that affects 1 in every 6 to 11,000 live births. This autosomal recessive disorder is caused by homozygous deletion or mutation of the SMN1 gene (survival motor neuron). As a backup, the SMN1 gene has the SMN2 gene, which produces only 10% of the functional SMN protein. Nusinersen and risdiplam, the first FDA-approved medications, act as SMN2 pre-mRNA splicing modifiers and enhance the quantity of SMN protein produced by this gene. The emergence of new therapies for SMA has increased the demand for good prognostic and pharmacodynamic (response) biomarkers in SMA. This article discusses current molecular diagnostic, prognostic, and pharmacodynamic biomarkers that could be assessed in SMA patients\u2019 body fluids. Although various proteomic, genetic, and epigenetic biomarkers have been explored in SMA patients, more research is needed to uncover new prognostic and pharmacodynamic biomarkers (or a combination of biomarkers).<\/jats:p>","DOI":"10.3390\/jcm12155060","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:24:24Z","timestamp":1690881864000},"page":"5060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Molecular Biomarkers for the Diagnosis, Prognosis, and Pharmacodynamics of Spinal Muscular Atrophy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6235-7993","authenticated-orcid":false,"given":"Marija","family":"Babi\u0107","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Banovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Bere\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7753-9640","authenticated-orcid":false,"given":"Tea","family":"Bani\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4223-4190","authenticated-orcid":false,"given":"Mirjana","family":"Babi\u0107 Leko","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-8154","authenticated-orcid":false,"given":"Monika","family":"Ulamec","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Clinical Hospital Sestre Milosrdnice Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Pathology, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Junakovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janja","family":"Kopi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadranka","family":"Serti\u0107","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Biochemistry, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"},{"name":"Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Bari\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6339-9261","authenticated-orcid":false,"given":"Goran","family":"\u0160imi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3233\/JND-190428","article-title":"One Year of Newborn Screening for SMA\u2014Results of a German Pilot Project","volume":"6","author":"Vill","year":"2019","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.semcdb.2014.04.026","article-title":"SMN control of RNP assembly: From post-transcriptional gene regulation to motor neuron disease","volume":"32","author":"Li","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1007\/s00018-018-2849-1","article-title":"The role of survival motor neuron protein (SMN) in protein homeostasis","volume":"75","author":"Chaytow","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2329048X2110087","DOI":"10.1177\/2329048X211008725","article-title":"Spinal Muscular Atrophy: The Use of Functional Motor Scales in the Era of Disease-Modifying Treatment","volume":"8","author":"Pierzchlewicz","year":"2021","journal-title":"Child Neurol. Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.nmd.2017.11.005","article-title":"Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care","volume":"28","author":"Mercuri","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.nmd.2009.11.014","article-title":"The Children\u2019s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): Test development and reliability","volume":"20","author":"Glanzman","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S1090-3798(03)00060-6","article-title":"The Hammersmith functional motor scale for children with spinal muscular atrophy: A scale to test ability and monitor progress in children with limited ambulation","volume":"7","author":"Main","year":"2003","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1177\/0883073811420294","article-title":"Validation of the Expanded Hammersmith Functional Motor Scale in spinal muscular atrophy type II and III","volume":"26","author":"Glanzman","year":"2011","journal-title":"J. Child Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1016\/S0140-6736(08)60921-6","article-title":"Spinal muscular atrophy","volume":"371","author":"Lunn","year":"2008","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1006\/geno.1996.0147","article-title":"Structure and organization of the human survival motor neurone (SMN) gene","volume":"32","author":"Lefebvre","year":"1996","journal-title":"Genomics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00439-002-0828-x","article-title":"Genetic testing and risk assessment for spinal muscular atrophy (SMA)","volume":"111","author":"Ogino","year":"2002","journal-title":"Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1086\/338627","article-title":"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","volume":"70","author":"Schwarzer","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3988\/jcn.2017.13.1.27","article-title":"Genotype-Phenotype Correlation of SMN1 and NAIP Deletions in Korean Patients with Spinal Muscular Atrophy","volume":"13","author":"Ahn","year":"2017","journal-title":"J. Clin. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s43042-019-0044-z","article-title":"Genetic pattern of SMN1, SMN2, and NAIP genes in prognosis of SMA patients","volume":"21","author":"Hassan","year":"2020","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.nmd.2011.03.009","article-title":"Plastin 3 expression in discordant spinal muscular atrophy (SMA) siblings","volume":"21","author":"Bernal","year":"2011","journal-title":"Neuromuscul. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1126\/science.1155085","article-title":"Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy","volume":"320","author":"Oprea","year":"2008","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.ajhg.2016.07.014","article-title":"The Power of Human Protective Modifiers: PLS3 and CORO1C Unravel Impaired Endocytosis in Spinal Muscular Atrophy and Rescue SMA Phenotype","volume":"99","author":"Hosseinibarkooie","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/BF01776636","article-title":"Zwei fr\u00fchinfantile heredit\u00e4re F\u00e4lle von progressiver Muskelatrophie unter dem Bilde der Dystrophie, aber anf neurotischer Grundlage","volume":"22","author":"Werdnig","year":"1891","journal-title":"Arch. f\u00fcr Psychiatr. und Nervenkrankh."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00401-008-0411-1","article-title":"Pathogenesis of proximal autosomal recessive spinal muscular atrophy","volume":"116","year":"2008","journal-title":"Acta Neuropathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00401-007-0327-1","article-title":"Abnormal motoneuron migration, differentiation, and axon outgrowth in spinal muscular atrophy","volume":"115","author":"Mladinov","year":"2008","journal-title":"Acta Neuropathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1212\/WNL.0b013e3182749eca","article-title":"Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3","volume":"79","author":"Wadman","year":"2012","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/tnsci-2017-0001","article-title":"ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy","volume":"8","author":"Ottesen","year":"2017","journal-title":"Transl. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1016\/S0140-6736(16)31408-8","article-title":"Treatment of infantile-onset spinal muscular atrophy with nusinersen: A phase 2, open-label, dose-escalation study","volume":"388","author":"Finkel","year":"2016","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fneur.2020.00045","article-title":"The Need for SMN-Independent Treatments of Spinal Muscular Atrophy (SMA) to Complement SMN-Enhancing Drugs","volume":"11","author":"Hensel","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/bcp.13786","article-title":"A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier","volume":"85","author":"Sturm","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.nbd.2008.10.003","article-title":"Biomarkers of Alzheimer\u2019s disease","volume":"35","author":"Fagan","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.bbadis.2008.07.008","article-title":"Peptides and proteins in plasma and cerebrospinal fluid as biomarkers for the prediction, diagnosis, and monitoring of therapeutic efficacy of Alzheimer\u2019s disease","volume":"1782","author":"Aluise","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/nature08538","article-title":"Multimodal techniques for diagnosis and prognosis of Alzheimer\u2019s disease","volume":"461","author":"Perrin","year":"2009","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"(1998). The Ronald and Nancy Reagan Research Institute of the Alzheimer\u2019s Association and the National Institute on Aging Working Group Consensus report of the Working Group on: \u201cMolecular and Biochemical Markers of Alzheimer\u2019s Disease\u201d. Neurobiol. Aging, 19, 109\u2013116.","DOI":"10.1016\/S0197-4580(98)00022-0"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/nrd3115","article-title":"Biomarkers for Alzheimer\u2019s disease: Academic, industry and regulatory perspectives","volume":"9","author":"Hampel","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrneurol.2010.4","article-title":"Cerebrospinal fluid and plasma biomarkers in Alzheimer\u2019s disease","volume":"6","author":"Blennow","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1602\/neurorx.1.2.182","article-title":"Biomarkers: Potential uses and limitations","volume":"1","author":"Mayeux","year":"2004","journal-title":"NeuroRx"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Finkel, R.S., Crawford, T.O., Swoboda, K.J., Kaufmann, P., Juhasz, P., Li, X., Guo, Y., Li, R.H., Trachtenberg, F., and Forrest, S.J. (2012). Candidate proteins, metabolites and transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA) clinical study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035462"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/acn3.406","article-title":"Longitudinal characterization of biomarkers for spinal muscular atrophy","volume":"4","author":"Bonati","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/ana.25101","article-title":"Natural history of infantile-onset spinal muscular atrophy","volume":"82","author":"Kolb","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11772719211035644","DOI":"10.1177\/11772719211035643","article-title":"Update on Biomarkers in Spinal Muscular Atrophy","volume":"16","author":"Pino","year":"2021","journal-title":"Biomark. Insights"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1242\/jcs.104729","article-title":"Neurofilaments at a glance","volume":"125","author":"Yuan","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1002\/acn3.51449","article-title":"Serum neurofilament light chain in pediatric spinal muscular atrophy patients and healthy children","volume":"8","author":"Nitz","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3233\/JND-220789","article-title":"Spinal Muscular Atrophy\u2014Is Newborn Screening Too Late for Children with Two SMN2 Copies?","volume":"9","author":"Schwartz","year":"2022","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1136\/jnnp-2018-319190","article-title":"Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: A meta-analysis of case-control studies","volume":"90","author":"Martin","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_42","first-page":"e12005","article-title":"Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer\u2019s disease","volume":"12","author":"Dhiman","year":"2020","journal-title":"Alzheimer Dement."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"651651","DOI":"10.3389\/fnins.2021.651651","article-title":"Cerebrospinal Fluid Neurofilament Light Chain (NfL) Predicts Disease Aggressiveness in Amyotrophic Lateral Sclerosis: An Application of the D50 Disease Progression Model","volume":"15","author":"Dreger","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s00726-011-0877-3","article-title":"The creatine kinase system and pleiotropic effects of creatine","volume":"40","author":"Wallimann","year":"2011","journal-title":"Amino Acids"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s40261-021-01071-0","article-title":"Cerebrospinal Fluid and Clinical Profiles in Adult Type 2-3 Spinal Muscular Atrophy Patients Treated with Nusinersen: An 18-Month Single-Centre Experience","volume":"41","author":"Milella","year":"2021","journal-title":"Clin. Drug Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1002\/acn3.51340","article-title":"Serum creatine kinase and creatinine in adult spinal muscular atrophy under nusinersen treatment","volume":"8","author":"Freigang","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e921","DOI":"10.1212\/WNL.0000000000008762","article-title":"Serum creatinine is a biomarker of progressive denervation in spinal muscular atrophy","volume":"94","author":"Alves","year":"2020","journal-title":"Neurology"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bianchi, L., Sframeli, M., Vantaggiato, L., Vita, G.L., Ciranni, A., Polito, F., Oteri, R., Gitto, E., Di Giuseppe, F., and Angelucci, S. (2021). Nusinersen Modulates Proteomics Profiles of Cerebrospinal Fluid in Spinal Muscular Atrophy Type 1 Patients. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094329"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e2000301","DOI":"10.1002\/pmic.202000301","article-title":"Label-free quantitative proteomic analysis of extracellular vesicles released from fibroblasts derived from patients with spinal muscular atrophy","volume":"21","author":"Roberto","year":"2021","journal-title":"Proteomics"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kobayashi, D.T., Shi, J., Stephen, L., Ballard, K.L., Dewey, R., Mapes, J., Chung, B., McCarthy, K., Swoboda, K.J., and Crawford, T.O. (2013). SMA-MAP: A plasma protein panel for spinal muscular atrophy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060113"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/acn3.51579","article-title":"Response of plasma microRNAs to nusinersen treatment in patients with SMA","volume":"9","author":"Zaharieva","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e68054","DOI":"10.7554\/eLife.68054","article-title":"SMA-miRs (MiR-181a- 5p, -324-5p, and -451a) are overexpressed in spinal muscular atrophy skeletal muscle and serum samples","volume":"10","author":"Abiusi","year":"2021","journal-title":"Elife"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1002\/acn3.51092","article-title":"Whole-blood dysregulation of actin-cytoskeleton pathway in adult spinal muscular atrophy patients","volume":"7","author":"Siranosian","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s12031-010-9422-1","article-title":"Alpha-Synuclein Loss in Spinal Muscular Atrophy","volume":"43","author":"Acsadi","year":"2011","journal-title":"J. Mol. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1186\/s13023-021-02075-x","article-title":"1H-NMR-based metabolic profiling identifies non-invasive diagnostic and predictive urinary fingerprints in 5q spinal muscular atrophy","volume":"16","author":"Saffari","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3233\/JND-210735","article-title":"Neurofilament Levels in CSF and Serum in an Adult SMA Cohort Treated with Nusinersen","volume":"9","author":"Rich","year":"2022","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"982760","DOI":"10.3389\/fncel.2022.982760","article-title":"Identification of a cytokine profile in serum and cerebrospinal fluid of pediatric and adult spinal muscular atrophy patients and its modulation upon nusinersen treatment","volume":"16","author":"Bonanno","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-021-01961-8","article-title":"Increased chitotriosidase 1 concentration following nusinersen treatment in spinal muscular atrophy","volume":"16","author":"Freigang","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1002\/acn3.51377","article-title":"Increased systemic HSP70B levels in spinal muscular atrophy infants","volume":"8","author":"Eichelberger","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s00415-019-09547-y","article-title":"Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen","volume":"267","author":"Wurster","year":"2020","journal-title":"J. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1111\/jcmm.14939","article-title":"Nusinersen treatment and cerebrospinal fluid neurofilaments: An explorative study on Spinal Muscular Atrophy type 3 patients","volume":"24","author":"Faravelli","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1007\/s00415-019-09389-8","article-title":"NFL is a marker of treatment response in children with SMA treated with nusinersen","volume":"266","author":"Olsson","year":"2019","journal-title":"J. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/acn3.779","article-title":"Neurofilament as a potential biomarker for spinal muscular atrophy","volume":"6","author":"Darras","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Otsuki, N., Arakawa, R., Kaneko, K., Aoki, R., Arakawa, M., and Saito, K. (2018). A new biomarker candidate for spinal muscular atrophy: Identification of a peripheral blood cell population capable of monitoring the level of survival motor neuron protein. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201764"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-14313-z","article-title":"Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy","volume":"7","author":"Nash","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Wadman, R.I., Stam, M., Jansen, M.D., Van Der Weegen, Y., Wijngaarde, C.A., Harschnitz, O., Sodaar, P., Braun, K.P.J., Dooijes, D., and Lemmink, H.H. (2016). A Comparative Study of SMN Protein and mRNA in Blood and Fibroblasts in Patients with Spinal Muscular Atrophy and Healthy Controls. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167087"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Zaworski, P., Von Herrmann, K.M., Taylor, S., Sunshine, S.S., Mccarthy, K., Risher, N., Newcomb, T., Weetall, M., Prior, T.W., and Swoboda, K.J. (2016). SMN Protein Can Be Reliably Measured in Whole Blood with an Electrochemiluminescence (ECL) Immunoassay: Implications for Clinical Trials. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150640"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Czech, C., Tang, W., Bugawan, T., Mano, C., Horn, C., Iglesias, V.A., Fr\u00f6hner, S., Zaworski, P.G., Paushkin, S., and Chen, K. (2015). Biomarker for Spinal Muscular Atrophy: Expression of SMN in Peripheral Blood of SMA Patients and Healthy Controls. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139950"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.bbrc.2014.09.087","article-title":"A novel evaluation method of survival motor neuron protein as a biomarker of spinal muscular atrophy by imaging flow cytometry","volume":"453","author":"Arakawa","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gm498","article-title":"Label-free proteomics identifies Calreticulin and GRP75\/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy","volume":"5","author":"Mutsaers","year":"2013","journal-title":"Genome Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/ejhg.2012.233","article-title":"Clinical and molecular cross-sectional study of a cohort of adult type III spinal muscular atrophy patients: Clues from a biomarker study","volume":"21","author":"Tiziano","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Crawford, T.O., Paushkin, S.V., Kobayashi, D.T., Forrest, S.J., Joyce, C.L., Finkel, R.S., Kaufmann, P., Swoboda, K.J., Tiziano, D., and Lomastro, R. (2012). Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033572"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Zheleznyakova, G.Y., Kiselev, A.V., Vakharlovsky, V.G., Rask-Andersen, M., Chavan, R., Egorova, A.A., Schi\u00f6th, H.B., and Baranov, V.S. (2011). Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III. BMC Med. Genet., 12.","DOI":"10.1186\/1471-2350-12-96"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kobayashi, D.T., Olson, R.J., Sly, L., Swanson, C.J., Chung, B., Naryshkin, N., Narasimhan, J., Bhattacharyya, A., Mullenix, M., and Chen, K.S. (2011). Utility of survival motor neuron ELISA for spinal muscular atrophy clinical and preclinical analyses. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024269"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1212\/01.wnl.0000201929.56928.13","article-title":"SMN mRNA and protein levels in peripheral blood: Biomarkers for SMA clinical trials","volume":"66","author":"Sumner","year":"2006","journal-title":"Neurology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3233\/JND-230012","article-title":"Full-Length SMN Transcript in Extracellular Vesicles as Biomarker in Individuals with Spinal Muscular Atrophy Type 2 Treated with Nusinersen","volume":"10","author":"Trifunov","year":"2023","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1111\/ene.15331","article-title":"Cathepsin D as biomarker in cerebrospinal fluid of nusinersen-treated patients with spinal muscular atrophy","volume":"29","author":"Schorling","year":"2022","journal-title":"Eur. J. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1002\/acn3.51562","article-title":"Scientific rationale for a higher dose of nusinersen","volume":"9","author":"Finkel","year":"2022","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8419","DOI":"10.1111\/jcmm.16802","article-title":"Evaluation of putative CSF biomarkers in paediatric spinal muscular atrophy (SMA) patients before and during treatment with nusinersen","volume":"25","author":"Johannsen","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.braindev.2019.12.006","article-title":"Intrathecal nusinersen treatment after ventriculo-peritoneal shunt placement: A case report focusing on the neurofilament light chain in cerebrospinal fluid","volume":"42","author":"Tozawa","year":"2020","journal-title":"Brain Dev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4725","DOI":"10.1212\/WNL.94.15_supplement.4725","article-title":"Effect of Nusinsersen in an Adult SMA Cohort: CSF Biomarkers and RULM (4725)","volume":"94","author":"Quinn","year":"2020","journal-title":"Neurology"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"\u0160imi\u0107, G., Vuki\u0107, V., Babi\u0107, M., Banovi\u0107, M., Bere\u010di\u0107, I., \u0160pani\u0107, E., Zub\u010di\u0107, K., Golubi\u0107, A.T., Bari\u0161i\u0107 Kutija, M., and Merkler \u0160orgi\u0107, A. (CNS Neurosci. Ther., 2022). Total tau in cerebrospinal fluid detects treatment responders among spinal muscular atrophy types 1-3 patients treated with nusinersen, CNS Neurosci. Ther., Early View.","DOI":"10.1111\/cns.14051"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/mus.27425","article-title":"Nusinersen by subcutaneous intrathecal catheter for symptomatic spinal muscular atrophy patients with complex spine anatomy","volume":"65","author":"Carson","year":"2022","journal-title":"Muscle Nerve"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3233\/JND-190416","article-title":"Safety and Treatment Effects of Nusinersen in Longstanding Adult 5q-SMA Type 3\u2014A Prospective Observational Study","volume":"6","author":"Walter","year":"2019","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"\u0160imi\u0107, G., Babi\u0107 Leko, M., Wray, S., Harrington, C., Delalle, I., Jovanov-Milo\u0161evi\u0107, N., Ba\u017eadona, D., Bu\u00e9e, L., de Silva, R., and Di Giovanni, G. (2016). Tau Protein Hyperphosphorylation and Aggregation in Alzheimer\u2019s Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Biomolecules, 6.","DOI":"10.3390\/biom6010006"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Totzeck, A., Stolte, B., Kizina, K., Bolz, S., Schlag, M., Thimm, A., Kleinschnitz, C., and Hagenacker, T. (2019). Neurofilament Heavy Chain and Tau Protein Are Not Elevated in Cerebrospinal Fluid of Adult Patients with Spinal Muscular Atrophy during Loading with Nusinersen. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215397"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1042\/BJ20060195","article-title":"Calcium-dependent and -independent interactions of the S100 protein family","volume":"396","author":"Shaw","year":"2006","journal-title":"Biochem. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1875044301205010001","article-title":"Role of chitotriosidase (chitinase 1) under normal and disease conditions","volume":"5","author":"Kanneganti","year":"2012","journal-title":"J. Epithel. Biol. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.braindev.2022.09.008","article-title":"Evaluation of cerebrospinal fluid biomarkers in pediatric patients with spinal muscular atrophy","volume":"45","author":"Kobayashi","year":"2023","journal-title":"Brain Dev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1002\/mus.27212","article-title":"Is cerebrospinal fluid amyloid-\u03b242 a promising biomarker of response to nusinersen in adult spinal muscular atrophy patients?","volume":"63","author":"Introna","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s13311-022-01305-9","article-title":"CSF IL-8 Associated with Response to Gene Therapy in a Case Series of Spinal Muscular Atrophy","volume":"20","author":"Verma","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1023\/A:1007677003387","article-title":"Glial fibrillary acidic protein: GFAP-thirty-one years (1969\u20132000)","volume":"25","author":"Eng","year":"2000","journal-title":"Neurochem. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s43856-023-00256-2","article-title":"Nusinersen mitigates neuroinflammation in severe spinal muscular atrophy patients","volume":"3","author":"Nuzzo","year":"2023","journal-title":"Commun. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ejpn.2022.12.003","article-title":"Inflammatory markers in cerebrospinal fluid of paediatric spinal muscular atrophy patients receiving nusinersen treatment","volume":"42","author":"Scheijmans","year":"2023","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/mus.27731","article-title":"Cerebrospinal fluid characteristics of patients treated with intrathecal nusinersen for spinal muscular atrophy","volume":"66","author":"Orbach","year":"2022","journal-title":"Muscle Nerve"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3390\/brainsci11030367","article-title":"Cerebrospinal Fluid Parameters in Antisense Oligonucleotide-Treated Adult 5q-Spinal Muscular Atrophy Patients","volume":"11","author":"Osmanovic","year":"2021","journal-title":"Brain Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4667","DOI":"10.1007\/s00415-021-10569-8","article-title":"Nusinersen treatment in adult patients with spinal muscular atrophy: A safety analysis of laboratory parameters","volume":"268","author":"Stolte","year":"2021","journal-title":"J. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/jnc.14953","article-title":"Cerebrospinal fluid proteomic profiling in nusinersen-treated patients with spinal muscular atrophy","volume":"153","author":"Kessler","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.3389\/fneur.2019.01179","article-title":"Routine Cerebrospinal Fluid (CSF) Parameters in Patients With Spinal Muscular Atrophy (SMA) Treated With Nusinersen","volume":"10","author":"Wurster","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1111\/ene.15382","article-title":"Muscle microRNAs in the cerebrospinal fluid predict clinical response to nusinersen therapy in type II and type III spinal muscular atrophy patients","volume":"29","author":"Magen","year":"2022","journal-title":"Eur. J. Neurol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/hmg\/ddab365","article-title":"Assessment of cerebral spinal fluid biomarkers and microRNA-mediated disease mechanisms in spinal muscular atrophy patient samples","volume":"31","author":"Welby","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Bonanno, S., Marcuzzo, S., Malacarne, C., Giagnorio, E., Masson, R., Zanin, R., Arnoldi, M.T., Andreetta, F., Simoncini, O., and Venerando, A. (2020). Circulating MyomiRs as Potential Biomarkers to Monitor Response to Nusinersen in Pediatric SMA Patients. Biomedicines, 8.","DOI":"10.3390\/biomedicines8020021"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Errico, F., Marino, C., Grimaldi, M., Nuzzo, T., Bassareo, V., Valsecchi, V., Panicucci, C., Di Schiavi, E., Mazza, T., and Bruno, C. (2022). Nusinersen Induces Disease-Severity-Specific Neurometabolic Effects in Spinal Muscular Atrophy. Biomolecules, 12.","DOI":"10.3390\/biom12101431"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s00415-020-10223-9","article-title":"Nusinersen treatment significantly improves hand grip strength, hand motor function and MRC sum scores in adult patients with spinal muscular atrophy types 3 and 4","volume":"268","author":"Goosens","year":"2021","journal-title":"J. Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1212\/WNL.0000000000002445","article-title":"Results from a phase 1 study of nusinersen (ISIS-SMNRx) in children with spinal muscular atrophy","volume":"86","author":"Chiriboga","year":"2016","journal-title":"Neurology"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Glascock, J., Darras, B.T., Crawford, T.O., Sumner, C.J., Kolb, S.J., DiDonato, C., Elsheikh, B., Howell, K., Farwell, W., and Valente, M. (2023). Identifying Biomarkers of Spinal Muscular Atrophy for Further Development. J. Neuromuscul. Dis., 1\u201318.","DOI":"10.3233\/JND-230054"},{"key":"ref_107","first-page":"e36197","article-title":"Gene Therapy for Spinal Muscular Atrophy (SMA): A Review of Current Challenges and Safety Considerations for Onasemnogene Abeparvovec (Zolgensma)","volume":"15","author":"Ogbonmide","year":"2023","journal-title":"Cureus"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e524","DOI":"10.1212\/CPJ.0000000000000872","article-title":"Molecular Biomarkers for Spinal Muscular Atrophy: A Systematic Review","volume":"11","author":"Garrison","year":"2021","journal-title":"Neurol. Clin. Pract."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/15\/5060\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:23:46Z","timestamp":1760127826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/15\/5060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,1]]},"references-count":108,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["jcm12155060"],"URL":"https:\/\/doi.org\/10.3390\/jcm12155060","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,1]]}}}