Spinocerebellar ataxias (SCAs) represent a large group of hereditary degenerative diseases of the nervous system, in particular the cerebellum, and other systems that manifest with a variety of progressive motor, cognitive, and behavioral deficits with the leading symptom of cerebellar ataxia. SCAs often lead to severe impairments of the patient’s functioning, quality of life, and life expectancy. For SCAs, there are no proven effective pharmacotherapies that improve the symptoms or substantially delay disease progress, i.e., disease-modifying therapies. To study SCA pathogenesis and potential therapies, animal models have been widely used and are an essential part of pre-clinical research. They mainly include mice, but also other vertebrates and invertebrates. Each animal model has its strengths and weaknesses arising from model animal species, type of genetic manipulation, and similarity to human diseases. The types of murine and non-murine models of SCAs, their contribution to the investigation of SCA pathogenesis, pathological phenotype, and therapeutic approaches including their advantages and disadvantages are reviewed in this paper. There is a consensus among the panel of experts that (1) animal models represent valuable tools to improve our understanding of SCAs and discover and assess novel therapies for this group of neurological disorders characterized by diverse mechanisms and differential degenerative progressions, (2) thorough phenotypic assessment of individual animal models is required for studies addressing therapeutic approaches, (3) comparative studies are needed to bring pre-clinical research closer to clinical trials, and (4) mouse models complement cellular and invertebrate models which remain limited in terms of clinical translation for complex neurological disorders such as SCAs.
|Original language||English (US)|
|Number of pages||30|
|Early online date||Aug 10 2021|
|State||Published - Aug 10 2021|
Bibliographical noteFunding Information:
The work on this article was supported by the following grants and projects: Charles University Research Fund (project number Q39 and project no. CZ.02.1.01/0.0/0.0/16_019/0000787) “Fighting INfectious Diseases,” awarded by the Ministry of Education, Youth and Sports of the Czech Republic, financed from the European Regional Development Fund (Jan Cendelin, Filip Tichanek, and Jan Tuma); R01 NS197387, R01NS109077, National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) (Marija Cvetanovic); Brain/MINDS from Japan Agency for Medical Research and development, AMED (Grant Number JP20dm0207057), KAKENHI (Grant Number 18H02521) (Hirokazu Hirai); grants R37NS033123, R21NSNS103009, and UO1NS103883 from the National Institutes of Health (USA) (Stefan M. Pulst); (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) grants R21NS103009, R01NS097903, R37NS033123, and U01NS103883 (Mandi Gandelman)Gandelman); and National Institutes of Health/National Institute of Neurological Disorders and Stroke grants RO1-NS022920 and RO1-NS045667 (Harry T. Orr).
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
- Spinocerebellar ataxias