1. Autosomal Recessive Cerebellar Ataxias: Paving the Way toward Targeted Molecular Therapies
- Author
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Matthis Synofzik, Hélène Puccio, Ludger Schöls, Fanny Mochel, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Subjects
0301 basic medicine ,Cerebellum ,methods [Translational Research, Biomedical] ,Ataxia ,Cerebellar Ataxia ,DNA repair ,pathways ,translation ,Genomics ,Translational research ,Biology ,pathology [Cerebellar Ataxia] ,therapy [Cerebellar Ataxia] ,Translational Research, Biomedical ,03 medical and health sciences ,0302 clinical medicine ,methods [Genetic Therapy] ,genomics ,medicine ,Animals ,Humans ,genetics ,methods [Molecular Targeted Therapy] ,Molecular Targeted Therapy ,ddc:610 ,methods [Translational Medical Research] ,therapy ,Clinical Trials as Topic ,treatment ,genetics [Cerebellar Ataxia] ,General Neuroscience ,ataxia ,Genetic Therapy ,trial ,biology.organism_classification ,3. Good health ,Transplantation ,Arcas ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,classification ,Mutation ,medicine.symptom ,Stem cell ,autosomal-recessive ataxias ,Neuroscience ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery - Abstract
Autosomal-recessive cerebellar ataxias (ARCAs) comprise a heterogeneous group of rare degenerative and metabolic genetic diseases that share the hallmark of progressive damage of the cerebellum and its associated tracts. This Review focuses on recent translational research in ARCAs and illustrates the steps from genetic characterization to preclinical and clinical trials. The emerging common pathways underlying ARCAs include three main clusters: mitochondrial dysfunction, impaired DNA repair, and complex lipid homeostasis. Novel ARCA treatments might target common hubs in pathogenesis by modulation of gene expression, stem cell transplantation, viral gene transfer, or interventions in faulty pathways. All these translational steps are addressed in current ARCA research, leading to the expectation that novel treatments for ARCAs will be reached in the next decade.
- Published
- 2019
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