Abstract
Since their introduction in 1996, animal models of multiple system atrophy (MSA) have generated important insights into pathogenesis and interventional therapies. Toxin and genetic approaches have been used alone or in combination to replicate progressive motor and non-motor symptoms reflecting human neuropathology. Here, we review these developments and discuss the advantages and limitations of the MSA animal models, as well as their application in preclinical target validation.
Highlights
Animal models allow researchers to study disease pathogenesis and progression in vivo
Researchers are conscious about the limitations of animal models of human disease in terms of their relevance to the human pathology and to the disease duration and progression, which may be difficult to replicate in a short-living rodent
It has become clear that living models provide a window to pathogenic mechanisms as well as identification and development of novel biomarker and therapeutic targets for multiple system atrophy (MSA)
Summary
Animal models allow researchers to study disease pathogenesis and progression in vivo. They offer the unique opportunity to screen therapeutic approaches in living organisms and justify their suitability for clinical trial initiation. Researchers are conscious about the limitations of animal models of human disease in terms of their relevance to the human pathology and to the disease duration and progression, which may be difficult to replicate in a short-living rodent. The applicability of MSA models for preclinical target validation is strengthened by functional outcome measures of progression, which would replicate the clinical features of the disease: (1) motor syndromes related to SND (parkinsonism) and OPCA (ataxia), as well as (2) non-motor presentation, including cardiovascular, urogenital, respiratory, gastrointestinal, sudomotor, and sleep disorders [1,2,3]. The approaches undertaken to achieve the goal of creating a relevant MSA animal model range from neurotoxic to transgenic techniques
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