{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:17:42Z","timestamp":1777576662241,"version":"3.51.4"},"reference-count":118,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["ALG-01- 0145-FEDER-29480"],"award-info":[{"award-number":["ALG-01- 0145-FEDER-29480"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013465","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["22424"],"award-info":[{"award-number":["22424"]}],"id":[{"id":"10.13039\/100013465","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000346","name":"Ataxia UK","doi-asserted-by":"publisher","award":["ZUNIALGA"],"award-info":[{"award-number":["ZUNIALGA"]}],"id":[{"id":"10.13039\/501100000346","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polyglutamine spinocerebellar ataxias (PolyQ SCAs) are a group of 6 rare autosomal dominant diseases, which arise from an abnormal CAG repeat expansion in the coding region of their causative gene. These neurodegenerative ataxic disorders are characterized by progressive cerebellar degeneration, which translates into progressive ataxia, the main clinical feature, often accompanied by oculomotor deficits and dysarthria. Currently, PolyQ SCAs treatment is limited only to symptomatic mitigation, and no therapy is available to stop or delay the disease progression, which culminates with death. Over the last years, many promising gene therapy approaches were investigated in preclinical studies and could lead to a future treatment to stop or delay the disease development. Here, we summed up the most promising of these therapies, categorizing them in gene augmentation therapy, gene silencing strategies, and gene edition approaches. While several of the reviewed strategies are promising, there is still a gap from the preclinical results obtained and their translation to clinical studies. However, there is an increase in the number of approved gene therapies, as well as a constant development in their safety and efficacy profiles. Thus, it is expected that in a near future some of the promising strategies reviewed here could be tested in a clinical setting and if successful provide hope for SCAs patients.<\/jats:p>","DOI":"10.3390\/ijms22084249","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T21:59:49Z","timestamp":1618869589000},"page":"4249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Current Status of Gene Therapy Research in Polyglutamine Spinocerebellar Ataxias"],"prefix":"10.3390","volume":"22","author":[{"given":"Ricardo","family":"Afonso-Reis","sequence":"first","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve, 8005-139 Faro, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00eas T.","family":"Afonso","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve, 8005-139 Faro, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8312-5292","authenticated-orcid":false,"given":"Cl\u00e9vio","family":"N\u00f3brega","sequence":"additional","affiliation":[{"name":"ABC-RI, Algarve Biomedical Center Research Institute, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Champalimaud Research Program, Champalimaud Center for the Unknown, 1400-038 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41572-019-0074-3","article-title":"Spinocerebellar ataxia","volume":"5","author":"Klockgether","year":"2019","journal-title":"Nat. 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