4fb73e59f6ff773595b6bfd8e9690887 pmc_10136823.pdf e00caba1cbf48e7c617f28ae40a818d838e1ef5c pmc_10136823.pdf f8f0881abe527650773fe30bfb377e6a7926224c9b627044c4b8869734b456d1 pmc_10136823.pdf Title: Biofluid Biomarkers in the Prognosis of Amyotrophic Lateral Sclerosis: Recent Developments and Therapeutic Applications Subject: Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons for which effective therapies are lacking. One of the most explored areas of research in ALS is the discovery and validation of biomarkers that can be applied to clinical practice and incorporated into the development of innovative therapies. The study of biomarkers requires an adequate theoretical and operational framework, highlighting the “fit-for-purpose” concept and distinguishing different types of biomarkers based on common terminology. In this review, we aim to discuss the current status of fluid-based prognostic and predictive biomarkers in ALS, with particular emphasis on those that are the most promising ones for clinical trial design and routine clinical practice. Neurofilaments in cerebrospinal fluid and blood are the main prognostic and pharmacodynamic biomarkers. Furthermore, several candidates exist covering various pathological aspects of the disease, such as immune, metabolic and muscle damage markers. Urine has been studied less often and should be explored for its possible advantages. New advances in the knowledge of cryptic exons introduce the possibility of discovering new biomarkers. Collaborative efforts, prospective studies and standardized procedures are needed to validate candidate biomarkers. A combined biomarkers panel can provide a more detailed disease status. Keywords: amyotrophic lateral sclerosis (ALS); biomarker; prognosis; pharmacodynamic biomarker; neurofilament light (NfL) protein; neuroinflammation; genetics Author: Daniel Sanchez-Tejerina, Arnau Llaurado, Javier Sotoca, Veronica Lopez-Diego, Jose M. Vidal Taboada, Maria Salvado and Raul Juntas-Morales Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Apr 18 07:28:47 2023 CEST ModDate: Tue Apr 18 07:42:41 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 373855 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SBMXUO+VnURWPalladioL Type 1 Custom yes yes no 10 0 LYSCUV+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 CUSPMG+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 CFDKWB+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 PFKOHU+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 42 0 GFAWRG+CMSY10 Type 1 Builtin yes yes no 64 0 LDSSDS+EURM10 Type 1 Builtin yes yes no 92 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-08-08 02:25:32 CEST RepresentationInformation: pmc_10136823.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-08-01 02:34:16 CEST Size: 373855 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 481 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Biomarkers in ALS: Categories, Conceptualization and Rational Application Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Fluid-Based Biomarkers in ALS: The Importance of the Study Sampling Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Recent Developments of ALS Prognostic, Predictive and Response Biomarkers in Biological Fluids Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: Neurofilaments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Neuroinflammation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Metabolism Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Muscle Injury Biomarkers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Non-Coding micro-RNA (miRNA) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Specific Biomarkers in Genetic Subtypes of ALS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Urinay Biomarkers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: New Horizons in ALS Biomarker Research: An Insight into the Pathology Associated with TDP-43 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Info: Title: Biofluid Biomarkers in the Prognosis of Amyotrophic Lateral Sclerosis: Recent Developments and Therapeutic Applications Author: Daniel Sanchez-Tejerina, Arnau Llaurado, Javier Sotoca, Veronica Lopez-Diego, Jose M. Vidal Taboada, Maria Salvado and Raul Juntas-Morales Subject: Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons for which effective therapies are lacking. One of the most explored areas of research in ALS is the discovery and validation of biomarkers that can be applied to clinical practice and incorporated into the development of innovative therapies. The study of biomarkers requires an adequate theoretical and operational framework, highlighting the “fit-for-purpose” concept and distinguishing different types of biomarkers based on common terminology. In this review, we aim to discuss the current status of fluid-based prognostic and predictive biomarkers in ALS, with particular emphasis on those that are the most promising ones for clinical trial design and routine clinical practice. Neurofilaments in cerebrospinal fluid and blood are the main prognostic and pharmacodynamic biomarkers. Furthermore, several candidates exist covering various pathological aspects of the disease, such as immune, metabolic and muscle damage markers. Urine has been studied less often and should be explored for its possible advantages. New advances in the knowledge of cryptic exons introduce the possibility of discovering new biomarkers. Collaborative efforts, prospective studies and standardized procedures are needed to validate candidate biomarkers. A combined biomarkers panel can provide a more detailed disease status. Keywords: amyotrophic lateral sclerosis (ALS); biomarker; prognosis; pharmacodynamic biomarker; neurofilament light (NfL) protein; neuroinflammation; genetics Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Apr 18 07:28:47 CEST 2023 ModDate: Tue Apr 18 07:42:41 CEST 2023 ID: 0xbaccc243541b495563f86d3eca476ec5, 0xbaccc243541b495563f86d3eca476ec5 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: GFAWRG+CMSY10 FontSubset: true FirstChar: 15 LastChar: 15 FontDescriptor: FontName: GFAWRG+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: CUSPMG+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: CUSPMG+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CFDKWB+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: CFDKWB+URWPalladioL-Ital Flags: Symbolic FontBBox: 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Subtype: Link Rect: 419, 630, 456, 640 Checksum: 4b8f31b7 Type: CRC32 Checksum: 4fb73e59f6ff773595b6bfd8e9690887 Type: MD5 Checksum: e00caba1cbf48e7c617f28ae40a818d838e1ef5c Type: SHA-1