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Autosomal and X-Linked Degenerative Ataxias: From Genetics to Promising Therapeutics

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Trials for Cerebellar Ataxias

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

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Abstract

Autosomal recessive cerebellar ataxias (ARCAs) refer to a large group of neurodegenerative disorders mainly affecting the cerebellum and the nervous system. ARCAs are characterized by important genetic heterogeneity and complex phenotypes. Because of their rarity and heterogeneity, it is challenging to rapidly advance our understanding in addition to discovering viable symptomatic and, most importantly, disease-modifying treatments. Significant advances have been recently achieved regarding the genetic basis of autosomal recessive and X-linked cerebellar ataxias. Unfortunately, the pathophysiology of most ARCAs is poorly characterized. For most ARCAs, clinical management consists in supplying symptomatic treatments. However, many new therapeutic strategies have emerged. They range from reducing the debilitating effects of ARCAs to exploring curative strategies. The aim of this chapter is to discuss fundamental and novel genetic aspects of ARCAs and X-linked cerebellar ataxias, focusing specifically on the fragile X tremor ataxia syndrome (FXTAS). We summarize clinical features, pathophysiology, diagnosis, currently available therapies, and novel research for the most frequent ARCAs. We also present examples of how novel and cutting-edge therapeutic tools including the clustered regularly interspaced short palindromic repeats (CRISPR) approach, antisense oligonucleotides (ASOs), and stem cells may lead to disease-modifying and ultimately curative treatment for ARCAs. The emphasis is made on new and ongoing research for the most frequent ARCAs. We will discuss promising future therapeutic strategies as well.

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Authors and Affiliations

  1. LOEX, CHU de Quebec-Université Laval Research Center, Quebec, QC, Canada

    Anya Hadji, Aurélie Louit, Vincent Roy, Mathieu Blais, François Berthod, François Gros-Louis & Nicolas Dupré

  2. Department of Surgery, Faculty of Medicine, Université Laval, Quebec, QC, Canada

    Vincent Roy, François Berthod & François Gros-Louis

  3. Regenerative Medicine Axis, CHU de Québec-Université Laval Research Center, Quebec, QC, Canada

    Mathieu Blais, François Berthod & François Gros-Louis

  4. Department of Medicine, Faculty of Medicine, Université Laval, Quebec, QC, Canada

    Nicolas Dupré

  5. Neuroscience Axis, CHU de Québec-Université Laval Research Center, Quebec, QC, Canada

    Nicolas Dupré

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  1. Professor of Neurology, Shuang Ho Hospital, Taipei Medical University, Taipei, (Republic of China), Taiwan

    Bing-wen Soong

  2. Professor of Neuroanatomy, University of Mons and CHU-Charleroi, Charleroi, Belgium

    Mario Manto

  3. Paris Brain Institute, (Institut du Cerveau – ICM), CNRS INSERM, Sorbonne Université, APHP, Paris, France

    Alexis Brice

  4. Department of Neurology, Spencer Fox Eccles School of Medicine University of Utah, Salt Lake City, UT, USA

    Stefan M. Pulst

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Hadji, A. et al. (2023). Autosomal and X-Linked Degenerative Ataxias: From Genetics to Promising Therapeutics. In: Soong, Bw., Manto, M., Brice, A., Pulst, S.M. (eds) Trials for Cerebellar Ataxias. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-031-24345-5_5

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