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Although disease-modifying therapies have recently become available, reliable biomarkers for disease monitoring remain limited. This study aimed to identify potential biomarkers of disease severity and monitoring in SMA using an unbiased approach based on differential gene expression datasets. A meta-analysis of datasets from 15 studies in SMA mouse models identified genes differentially expressed in at least three studies. Of the 134 differentially expressed genes, 122 had human orthologs, with only two being CNS-specific and consistently altered across studies, including glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivity. Candidate gene expression was subsequently evaluated in two human datasets. GFAP and neurofilament light chain (NfL) serum levels were then measured in a case\u2013control study including 25 SMA patients (11 type 1, 14 types 2\/3) and 24 matched controls, followed by a 12-month cohort study of the SMA patients. GFAP levels in cerebrospinal fluid (CSF) were assessed in 14 patients before and up to 14 months after initiation of disease-modifying therapies. Serum GFAP levels were lower in SMA patients compared with controls (P = 0.014), but higher in those with SMA type 1 (P = 0.028) and in patients with two SMN2 copies (P = 0.03). Patients under disease-modifying treatment exhibited higher baseline GFAP levels (P = 0.01). CSF GFAP levels decreased after 14 months of treatment in SMA type 1 and in pre-symptomatic patients predicted to develop type 1 (P = 0.045). NfL levels were elevated in SMA patients, correlating with disease severity and SMN2 genotype, and further increased over 12 months. Taken together, this study, employing an unbiased biomarker discovery strategy, identified GFAP as a candidate biomarker for SMA. Clinical validation demonstrated reduced serum GFAP levels, which correlated with disease type, SMN2 copy number and treatment status. In SMA type 1, CSF GFAP levels declined over time with treatment. These findings implicate astrocytes in SMA-related neurodegeneration and support GFAP as a potential biomarker for the disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag350","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:53:39Z","timestamp":1789041219000},"source":"Crossref","is-referenced-by-count":0,"title":["Unbiased bioinformatic and clinical analysis identifies glial fibrillary acidic protein as a potential biomarker in spinal muscular atrophy"],"prefix":"10.1093","volume":"8","author":[{"given":"Karina L\u00facia","family":"Soares de Oliveira","sequence":"first","affiliation":[{"name":"Federal University of Rio Grande do Sul Graduate Program in Medicine, Medical Sciences, , Porto Alegre, RS 90035003 ,","place":["Brazil"]},{"name":"Clinical Neurogenetics Research Group, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur Carpeggiani","family":"Weber","sequence":"additional","affiliation":[{"name":"Clinical Neurogenetics Research Group, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele Michelin","family":"Becker","sequence":"additional","affiliation":[{"name":"Child Neurology Unit, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Silva de Almeida","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Neuromuscular Disease Center, Escola Bahiana de Medicina e Sa\u00fade P\u00fablica , Salvador, BA 40285001 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Let\u00edcia Amorim","family":"de Albuquerque","sequence":"additional","affiliation":[{"name":"Federal University of Rio Grande do Sul Graduate Program in Medicine, Medical Sciences, , Porto Alegre, RS 90035003 ,","place":["Brazil"]},{"name":"Clinical Neurogenetics Research Group, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia Kersting","family":"Chadanowicz","sequence":"additional","affiliation":[{"name":"Clinical Neurogenetics Research Group, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna C\u00e2mara","family":"Giudicelli","sequence":"additional","affiliation":[{"name":"Bioinformatics Core, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 ,","place":["Brazil"]},{"name":"Federal University of Rio Grande do Sul Graduate Program in Genetics and Molecular Biology, , Porto Alegre, RS 91501-970 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francieli","family":"Rohden","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio Grande do Sul Graduate Program in Biological Sciences: Biochemistry, , Porto Alegre, RS 90035-003 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Rigon","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio Grande do Sul Graduate Program in Biological Sciences: Biochemistry, , Porto Alegre, RS 90035-003 ,","place":["Brazil"]},{"name":"Universidade Federal do Rio Grande do Sul Graduate Program in Biological Sciences: Pharmacology and Therapeutics, , Porto Alegre, RS 90050170 ,","place":["Brazil"]},{"name":"Department of Pharmacology, Federal University of Rio Grande do Sul , Porto Alegre, RS 90050170 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thayne Woycinck","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Bioinformatics Core, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 ,","place":["Brazil"]},{"name":"Federal University of Rio Grande do Sul Graduate Program in Genetics and Molecular Biology, , Porto Alegre, RS 91501-970 ,","place":["Brazil"]},{"name":"Medical Genetics Service, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Siebert","sequence":"additional","affiliation":[{"name":"Unit of Laboratorial Research, Experimental Research Center, Hospital de Cl\u00ednicas de Porto Alegre (HCPA) , Porto Alegre, RS 90035903 ,","place":["Brazil"]},{"name":"Federal University of Rio Grande do Sul Graduate Program in Gastroenterology and Hepatology, , RS 90035003, Porto Alegre ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela C\u00e2mara Machado","family":"Costa","sequence":"additional","affiliation":[{"name":"Neuromuscular Disease Center, Escola Bahiana de Medicina e Sa\u00fade P\u00fablica , Salvador, BA 40285001 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1141-6573","authenticated-orcid":false,"given":"Jonas Alex","family":"Saute","sequence":"additional","affiliation":[{"name":"Federal University of Rio Grande do Sul Graduate Program in Medicine, Medical Sciences, , Porto Alegre, RS 90035003 ,","place":["Brazil"]},{"name":"Clinical Neurogenetics Research Group, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 ,","place":["Brazil"]},{"name":"Federal University of Rio Grande do Sul Graduate Program in Genetics and Molecular Biology, , Porto Alegre, RS 91501-970 ,","place":["Brazil"]},{"name":"Medical Genetics Service, Hospital de Cl\u00ednicas de Porto Alegre , Porto Alegre, RS 90035903 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