Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann-Pick disease, type C1.
Biol Open
; 11(4)2022 04 15.
Article
em En
| MEDLINE
| ID: mdl-35452076
ABSTRACT
Identifying meaningful predictors of therapeutic efficacy from preclinical studies is challenging. However, clinical manifestations occurring in both patients and mammalian models offer significant translational value. Many neurological disorders, including inherited, metabolic Niemann-Pick disease, type C (NPC), exhibit ataxia. Both individuals with NPC and murine models manifest ataxia, and investigational therapies impacting this phenotype in mice have been reported to slow disease progression in patients (e.g. miglustat, intrathecal 2-hydroxypropyl-beta-cyclodextrin, and acetyl-L-leucine). Reproducible phenotypic scoring of animal models can facilitate comparisons between genotypes, sexes, disease course, and therapies. Previously, other groups have developed a composite phenotypic scoring system (CPSS), which was subsequently used to distinguish strain-dependent phenotypes and, with modifications, to evaluate potential therapies. However, high inter-rater reliability is paramount to widespread use. We have created a comprehensive, easy-to-follow phenotypic assessment based on the CPSS and have verified its reproducibility using murine models of NPC disease. Application of this scoring system is not limited to NPC disease and may be applicable to other models of neurodegeneration exhibiting motor incoordination, thereby increasing its utility in translational studies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Niemann-Pick Tipo C
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article