517cc6234bd12d5ca6d434a6e96e12fa pmc_33670433.pdf da846136326c1fe1f83dd52d9fd45c9e17d29988 pmc_33670433.pdf b88a62ad97c65a7522ef8cd0b4f652c0203941cc1a43b7bc02007d234e440dfc pmc_33670433.pdf Title: Future Prospects of Gene Therapy for Friedreich’s Ataxia Subject: Friedreich’s ataxia is an autosomal recessive neurogenetic disease that is mainly associated with atrophy of the spinal cord and progressive neurodegeneration in the cerebellum. The disease is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein, which results in mitochondrial dysfunction. Currently, there is no effective treatment to delay neurodegeneration in Friedreich’s ataxia. A plausible therapeutic approach is gene therapy. Indeed, Friedreich’s ataxia mouse models have been treated with viral vectors en-coding for either FXN or neurotrophins, such as brain-derived neurotrophic factor showing promising results. Thus, gene therapy is increasingly consolidating as one of the most promising therapies. However, several hurdles have to be overcome, including immunotoxicity and pheno-toxicity. We review the state of the art of gene therapy in Friedreich’s ataxia, addressing the main challenges and the most feasible solutions for them. Keywords: gene therapy; neurodegeneration; Friedreich’s Ataxia; AAV; mouse models; preclinical studies; clinical trials Author: Gabriel Ocana-Santero, Javier Díaz-Nido and Saúl Herranz-Martín Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Feb 22 13:17:48 2021 CET ModDate: Mon Feb 22 13:22:33 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1165699 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- DRZUJM+VnURWPalladioL Type 1 Custom yes yes no 10 0 JRXSGX+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 QYJULM+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 ZTYIYZ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 LPYGPS+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 36 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 61 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 65 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 69 0 SRVVQU+CMSY10 Type 1 Builtin yes yes no 81 0 GOCQIR+EURM10 Type 1 Builtin yes yes no 85 0 IHGURL+EURM7 Type 1 Builtin yes yes no 118 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:28:39 CEST RepresentationInformation: pmc_33670433.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:09:04 CEST Size: 1165699 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 543 FreeObjects: 3 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: In Vivo Gene Therapy and AAV Vectors Destination: section.2 Item: Title: Routes of Administration for Central Nervous System Delivery Destination: section.3 Item: Title: Friedreich’s Ataxia Animal Models Destination: section.4 Item: Title: Gene Therapy in Friedreich’s Ataxia Destination: section.5 Item: Title: Discussion Destination: section.6 Item: Title: Conclusions Destination: section.7 Item: Title: References Destination: section.7 Info: Title: Future Prospects of Gene Therapy for Friedreich’s Ataxia Author: Gabriel Ocana-Santero, Javier Díaz-Nido and Saúl Herranz-Martín Subject: Friedreich’s ataxia is an autosomal recessive neurogenetic disease that is mainly associated with atrophy of the spinal cord and progressive neurodegeneration in the cerebellum. The disease is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein, which results in mitochondrial dysfunction. Currently, there is no effective treatment to delay neurodegeneration in Friedreich’s ataxia. A plausible therapeutic approach is gene therapy. Indeed, Friedreich’s ataxia mouse models have been treated with viral vectors en-coding for either FXN or neurotrophins, such as brain-derived neurotrophic factor showing promising results. Thus, gene therapy is increasingly consolidating as one of the most promising therapies. However, several hurdles have to be overcome, including immunotoxicity and pheno-toxicity. We review the state of the art of gene therapy in Friedreich’s ataxia, addressing the main challenges and the most feasible solutions for them. 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