Natural History of Spinocerebellar Ataxia Type 7 (SCA7)

脊髓小脑型共济失调7型是一种由ATXN7基因编码区CAG三核苷酸重复序列扩增引起的神经退行性疾病。它与其他常染色体显性遗传性脊髓小脑性共济失调的区别在于伴有视网膜变性。因此，视力丧失是影响这些患者生活质量的重要并发症，然而，目前的治疗仅限于改变生活方式。眼睛是潜在治疗研究的极佳目标，因为它具有相对免疫的特权，可以通过手术获得，而且很容易检查和成像。因此，在应用于其他中枢神经系统之前，在SCA7中建立眼部疾病治疗的概念验证是非常有吸引力的。虽然在全球各地的人群中已经报告了大量的病例报告或小病例系列，但分子证实的SCA7个体视网膜变性的纵向临床过程尚未被记录在案。通过这项研究，我们希望收集这些信息，为未来的临床试验做准备。 19名患者已经成功地完成了他们的基线评估，包括标准化的病史/眼科病史、完整的基线眼科检查以及色觉测试、视野测试、视网膜电描记术、心理生理学、眼科成像和眼动记录、神经学检查、神经成像、眼动记录和神经心理评估(如果能够参与)。年龄从15.6岁到62.8岁不等，有40到69个扩大的CAG重复序列(正常和18岁)和不同的疾病严重程度。最佳矫正视力在20/16到20/400之间，R=0.97p&lt；0.0001。视神经萎缩和视锥细胞视杆细胞营养不良均有不同程度的改变。随着患者继续登记和返回进行随访，我们希望完成进一步的纵向分析，并潜在地确定未来试验的临床结果衡量标准。

Spinocerebellar Ataxia Type 7 is a neurodegenerative disease caused by an expansion of a CAG trinucleotide repeat in the coding region of the ATXN7 gene. It is distinguished from other autosomal dominant spinocerebellar ataxias by its associated retinal degeneration. Vision loss is therefore a significant comorbidity affecting the quality of life of these patients however at this time, treatment is limited to lifestyle modification. The eye presents itself as an excellent target for research on potential therapies as it is relatively immune privileged, surgically accessible and easily examined and imaged. Establishing proof-of-concept for a therapy in ocular disease is therefore very attractive in SCA7 before application in other CNS systems. While numerous case reports or small case series have been reported in populations from across the globe, the longitudinal clinical course of retinal degeneration in molecularly-confirmed SCA7 individuals has not yet been documented. With this study, we hope to gather this information in anticipation of future clinical trials. 19 patients have successfully completed their baseline evaluations, including standardized medical/ophthalmic history, complete baseline eye examination as well as color vision testing, visual field testing, electroretinography, psychophysiology, ophthalmic imaging and eye movement recordings, neurology exam, neuroimaging, eye movement recordings and neuropsychological assessment if able to participate. Age ranging from 15.6 to 62.8 years enrolled with a range of 40 to 69 expanded CAG repeats (normal <18) and different levels of disease severity. Best corrected visual acuity has ranged from 20/16 to 20/400, with R=0.97, p<0.0001 correlation of acuity between eyes of a given participant. Optic atrophy and cone rod dystrophy were seen to varying degrees. As patients continue to enroll and return for follow up visits, we hope to complete further longitudinal analysis and potentially identify clinical outcome measures for future trials.