Emerging therapies in hereditary ataxias.
| Title: | Emerging therapies in hereditary ataxias. |
|---|---|
| Authors: | Eisel MLS; Department of Neurology and the Fixel Institute for Neurological Disorders, University of Florida College of Medicine, Gainesville, FL, USA.; Burns M; Department of Neurology and the Fixel Institute for Neurological Disorders, University of Florida College of Medicine, Gainesville, FL, USA.; Ashizawa T; Stanley H. Appel Department of Neurology, Weill Cornell Medicine at Houston Methodist Hospital, Houston, TX, USA.; Byrne B; Department of Pediatrics and the Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA.; Corti M; Department of Pediatrics and the Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA.; Subramony SH; Department of Neurology and the Fixel Institute for Neurological Disorders, University of Florida College of Medicine, Gainesville, FL, USA. Electronic address: s.subramony@neurology.ufl.edu. |
| Source: | Trends in molecular medicine [Trends Mol Med] 2025 Feb; Vol. 31 (2), pp. 181-194. Date of Electronic Publication: 2024 Aug 16. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 100966035 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1471-499X (Electronic) Linking ISSN: 14714914 NLM ISO Abbreviation: Trends Mol Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford, UK : Elsevier Science Ltd., c2001- |
| MeSH Terms: | Genetic Therapy*/methods ; Friedreich Ataxia*/therapy ; Friedreich Ataxia*/genetics ; Spinocerebellar Degenerations*/therapy ; Spinocerebellar Degenerations*/genetics; Humans ; Animals ; Gene Editing |
| Abstract: | Recent investigations have defined the pathophysiological basis of many hereditary ataxias (HAs), including loss-of-function as well as gain-of-function mechanisms at either the RNA or protein level. Preclinical studies have assessed gene editing, gene and protein replacement, gene enhancement, and gene knockdown strategies. Methodologies include viral vector delivery of genes, oligonucleotide therapies, cell-penetrating peptides, synthetic transcription factors, and technologies to deliver therapies to defined targets. In this review, we focus on Friedreich ataxia (FRDA) and the polyglutamine ataxias in which translational research is active. However, much remains to be done to identify safe and effective molecules, create ideal delivery methods, and perform innovative clinical trials to prove the safety and efficacy of treatments for these rare but devastating diseases.; (Copyright © 2024. Published by Elsevier Ltd.) |
| Competing Interests: | Declaration of interests S.H.S. has received research support from the following for conducting clinical trials and studies on disorders dealt with in this review: Reata Pharmaceuticals, Retrotope, PTC therapeutics, Biogen, Biohaven, NINDS NS UO 1, National Ataxia Foundation, and Friedreich Ataxia Research Alliance. T.A. has received research support from the following for conducting clinical trials and studies on disorders dealt with in this review: Biogen, Biohaven, and NINDS NS UO1. B.B., M.C., M.B., and M.E. have no conflicting interests to declare. |
| Contributed Indexing: | Keywords: RNA interference; clinical trials; genetic therapies; hereditary ataxia; oligonucleotides |
| Entry Date(s): | Date Created: 20240817 Date Completed: 20250423 Latest Revision: 20250514 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.molmed.2024.07.008 |
| PMID: | 39153956 |
| Database: | MEDLINE |
Journal Article; Review