脊髓小脑性共济失调(SCAs)是神经系统的一大类遗传性退行性疾病,尤其是小脑,和其他表现为各种渐进运动的系统,认知,以小脑共济失调为主要症状的行为缺陷。SCA通常会导致患者功能严重受损,生活质量,和预期寿命。对于SCA,没有被证明有效的药物疗法可以改善症状或大大延迟疾病进展,即,疾病修饰疗法。为了研究SCA的发病机制和潜在的治疗方法,动物模型已被广泛使用,是临床前研究的重要组成部分。它们主要包括老鼠,还有其他脊椎动物和无脊椎动物。每种动物模型都有其优势和劣势,源于模型动物物种,遗传操作的类型,与人类疾病相似。SCA的鼠和非鼠模型的类型,他们对SCA发病机制研究的贡献,病理表型,并对其治疗方法及其优缺点进行了综述。专家小组之间达成共识:(1)动物模型代表了有价值的工具,可以提高我们对SCA的理解,并发现和评估这组神经系统疾病的新疗法,其特征在于不同的机制和不同的退行性进展。(2)研究治疗方法需要对单个动物模型进行彻底的表型评估,(3)需要进行比较研究,以使临床前研究更接近临床试验,和(4)小鼠模型补充细胞和无脊椎动物模型,所述细胞和无脊椎动物模型在复杂神经障碍如SCA的临床翻译方面仍然有限。
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.