Natural History of Spinocerebellar Ataxia Type 7 (SCA7)

脊髓小脑共济失调7型是由ATXN 7基因编码区CAG三核苷酸重复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共济失调的区别在于其相关的视网膜变性。 因此，视力丧失是影响这些患者生活质量的重要合并症，但目前治疗仅限于改变生活方式。 眼睛是研究潜在疗法的一个很好的目标，因为它相对免疫特权，手术可及，易于检查和成像。 因此，在应用于其他CNS系统之前，在SCA 7中建立眼部疾病治疗的概念验证是非常有吸引力的。 虽然在来自地球仪的人群中报告了许多病例报告或小病例系列，但尚未记录经分子学证实的SCA 7个体中视网膜变性的纵向临床病程。 通过这项研究，我们希望收集这些信息，以期待未来的临床试验。 19例患者已成功完成基线评价，包括标准化病史/眼科史、完整的基线眼部检查以及色觉测试、视野测试、视网膜电图、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学评估（如果能够参与）。年龄范围为15.6至62.8岁，具有40至69个扩增CAG重复（正常<18）和不同疾病严重程度的范围。最佳矫正视力范围为20/16至20/400，R=0.97，p<0.0001，给定参与者眼睛之间的视力相关性。不同程度的视神经萎缩和视锥杆营养不良。随着患者继续入组并返回进行随访，我们希望完成进一步的纵向分析，并可能确定未来试验的临床结局指标。

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.