The Dog Model in the Spotlight: Legacy of a Trustful Cooperation.
J Neuromuscul Dis
; 6(4): 421-451, 2019.
Article
en En
| MEDLINE
| ID: mdl-31450509
ABSTRACT
Dogs have long been used as a biomedical model system and in particular as a preclinical proof of concept for innovative therapies before translation to humans. A recent example of the utility of this animal model is the promising myotubularin gene delivery in boys affected by X-linked centronuclear myopathy after successful systemic, long-term efficient gene therapy in Labrador retrievers. Mostly, this is due to unique features that make dogs an optimal system. The continuous emergence of spontaneous inherited disorders enables the identification of reliable complementary molecular models for human neuromuscular disorders (NMDs). Dogs' characteristics including size, lifespan and unprecedented medical care level allow a comprehensive longitudinal description of diseases. Moreover, the highly similar pathogenic mechanisms with human patients yield to translational robustness. Finally, interindividual phenotypic heterogeneity between dogs helps identifying modifiers and anticipates precision medicine issues.This review article summarizes the present list of molecularly characterized dog models for NMDs and provides an exhaustive list of the clinical and paraclinical assays that have been developed. This toolbox offers scientists a sensitive and reliable system to thoroughly evaluate neuromuscular function, as well as efficiency and safety of innovative therapies targeting these NMDs. This review also contextualizes the model by highlighting its unique genetic value, shaped by the long-term coevolution of humans and domesticated dogs. Because the dog is one of the most protected research animal models, there is considerable opposition to include it in preclinical projects, posing a threat to the use of this model. We thus discuss ethical issues, emphasizing that unlike many other models, the dog also benefits from its contribution to comparative biomedical research with a drastic reduction in the prevalence of morbid alleles in the breeding stock and an improvement in medical care.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Miopatías Estructurales Congénitas
/
Proteínas Tirosina Fosfatasas no Receptoras
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspecto:
Ethics
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Neuromuscul Dis
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS