{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:53:39Z","timestamp":1792364019206,"version":"4.4.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002108","name":"Friedreich's Ataxia Research Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Clinical trials in rare diseases as Friedreich ataxia (FRDA) offer special challenges, particularly when multiple treatments become ready for clinical testing. Regulatory health authorities have developed specific pathways for \u201corphan\u201d drugs allowing the use of a validated biomarker for initial approval. This study aimed to identify changes in cerebrospinal fluid (CSF) proteins occurring in FRDA patients that may be potential biomarkers in therapeutic trials. CSF was obtained from 5 FRDA patients (4 females, 1 male) from the Brussels site of the European Friedreich Ataxia Consortium for Translational Studies (EFACTS). Two patients were ambulatory, three used a wheelchair. Residual CSF samples from 19 patients who had had a lumbar puncture as part of a diagnostic workup were used as controls. All CSF samples had normal cells, total protein and glucose levels. Proteins were identified by label-free data-dependent acquisition mass spectrometry (MS) coupled to micro-high performance liquid chromatography. We found 172 differentially expressed proteins (DEPs) (92 up, 80 down) between FRDA patients and controls at <jats:italic>P<\/jats:italic> &amp;lt; 0.05, 34 DEPs (28 up, 6 down) at <jats:italic>P<\/jats:italic> &amp;lt; 0.0001. Remarkably, there was no overlap between FRDA patients and controls for seven upregulated and six downregulated DEPs. Represented pathways included extracellular matrix organization, signaling, the complement cascade, adhesion molecules, synaptic proteins, neurexins and neuroligins. This study supports the hypothesis that the quantitative analysis CSF proteins may provide robust biomarkers for clinical trials as well as shed light on pathogenic mechanisms. Interestingly, DEPs in FA patients CSF point to neurodegeneration and neuroinflammation processes that may respond to treatment.<\/jats:p>","DOI":"10.3389\/fnins.2022.885313","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T09:47:28Z","timestamp":1657705648000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Cerebrospinal Fluid Proteomics in Friedreich Ataxia Reveals Markers of Neurodegeneration and Neuroinflammation"],"prefix":"10.3389","volume":"16","author":[{"given":"Virginie","family":"Imbault","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Dionisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Naeije","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Communi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Pandolfo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich\u2019s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion.","volume":"271","author":"Campuzano","year":"1996","journal-title":"Science (New York, N.Y.)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.7554\/elife.30054","article-title":"Inducible and reversible phenotypes in a novel mouse model of Friedreich\u2019s Ataxia.","volume":"6","author":"Chandran","year":"2017","journal-title":"eLife"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1007\/s00415-020-09868-9863","article-title":"Neurofilament light chain as a potential biomarker of disease status in Friedreich ataxia.","volume":"267","author":"Clay","year":"2020","journal-title":"J. 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