{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T11:17:48Z","timestamp":1769944668235,"version":"3.49.0"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Introduction: Hereditary cerebellar ataxias (HCAs) are a heterogenous group of neurodegenerative disorders associated with severe disability. Treatment options are limited and overall restricted to symptomatic approaches, leading to poor prognoses. In recent years, there has been extensive research on gene suppression therapies (GSTs) as a new hope for disease-modifying strategies. In this article, we aim to perform a review of in vivo studies investigating the efficacy and safety profile of GSTs in HCAs. Methods: A structured PubMed\u00ae search on GSTs in HCAs from January 1993 up to October 2020 was performed. Inclusion and exclusion criteria were defined, and the selection process was conducted accordingly. The screening process was independently carried out by two authors and was initially based on title and abstract, followed by full-text reading. The risk-of-bias assessment was performed with SYRCLE\u2019s tool. A data extraction sheet was created to collect relevant information from each selected article. Results: The initial search yielded 262 papers, of which 239 were excluded. An additional article was obtained following reference scrutiny, resulting in a total of 24 articles for final analysis. Most studies were not clear on the tools used to assess bias. In SCA1, SCA2, MJD\/SCA3 and SCA7, RNA interference (iRNA) and antisense oligonucleotide (ASO) therapies proved to be well tolerated and effective in suppressing mutant proteins, improving neuropathological features and the motor phenotype. In SCA6, the phenotype was improved, but no investigation of adverse effects was performed. In FRDA, only the suppression efficacy of the electroporation of the clustered regularly interspaced short palindromic repeats associated with Cas9 enzyme system (CRISPR-Cas9) system was tested and confirmed. Conclusion: The literature reviewed suggests that GSTs are well tolerated and effective in suppressing the targeted proteins, improving neuropathological features and the motor phenotype in vivo. Nonetheless, there is no guarantee that these results are free of bias. Moreover, further investigation is still needed to clarify the GST effect on HCAs such as FRDA, SCA6 and SCA2.<\/jats:p>","DOI":"10.3390\/cells12071037","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T04:00:54Z","timestamp":1680062454000},"page":"1037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gene Suppression Therapies in Hereditary Cerebellar Ataxias: A Systematic Review of Animal Studies"],"prefix":"10.3390","volume":"12","author":[{"given":"Carolina","family":"Santos","sequence":"first","affiliation":[{"name":"Infectious Diseases Department, Centro Hospitalar Lisboa Ocidental, 1449-005 Lisboa, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Malheiro","sequence":"additional","affiliation":[{"name":"Neurology Department, Centro Hospitalar Universit\u00e1rio do Porto, 4099-001 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Correia","sequence":"additional","affiliation":[{"name":"Neurology Department, Centro Hospitalar Universit\u00e1rio do Porto, 4099-001 Porto, Portugal"},{"name":"ICBAS School of Medicine and Biomedical Sciences, Universidade do Porto, 4050-318 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6539-6398","authenticated-orcid":false,"given":"Joana","family":"Dam\u00e1sio","sequence":"additional","affiliation":[{"name":"Neurology Department, Centro Hospitalar Universit\u00e1rio do Porto, 4099-001 Porto, Portugal"},{"name":"CGPP, IBMC-Institute for Molecular and Cell Biology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"UnIGENe, IBMC-Institute for Molecular and Cell Biology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"ref_1","first-page":"673","article-title":"Hereditary ataxias: Overview","volume":"15","author":"Jayadev","year":"2013","journal-title":"Genet. 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