■脊髓小脑共济失调的基因治疗试验需要具有诊断和预后价值的可靠生物标志物。
■鉴定脊髓小脑共济失调7型(SCA7)携带者样品中的眼科生物标志物。
■本文提供了在巴黎进行的横断面自然史研究的基线数据,法国,2020年5月至2021年4月的罕见疾病参考中心。数据从2022年9月至12月进行了分析。包括15名成人ATXN7致病性扩张携带者(9名患有共济失调,6名患有共济失调),所有的共济失调评估和评级量表(SARA)评分为40分或更低的15分。巴黎大脑研究所招募了患者,所有联系的患者均接受参与研究。
■三次访问(基线,6个月,和12个月)是计划好的,包括神经系统检查(SARA和复合小脑功能严重程度评分),眼科检查(最佳矫正视力,显微视野,全场视网膜电图,光学相干层析成像,和眼底自发荧光成像),和神经丝轻链(NfL)测量。在这里,我们报告来自队列的基线眼科数据,并确定疾病评分和眼科结果之间是否存在相关性。
■在包括的15名SCA7携带者中(年龄中位数,38[18-60]岁;8名女性和7名男性),12显示圆锥或锥杆营养不良,CAG重复的数量与疾病严重程度相关(ρ,0.73,95%CI,0.34至0.90;P<.001)。两名患有视锥棒营养不良的患者表现出更高的重复次数和更高的共济失调评分(中位数[范围]SARA评分,9[7-15])与仅患有视锥营养不良的患者(中位数[范围]SARA评分,2[0-5]).外核层厚度与SARA评分(ρ,-0.88;95%CI,-0.96至-0.59;P<.001)和NfL水平(ρ,-0.87;95%CI,-0.86至0.96;P<.001)。此外,共济失调严重程度与视力(ρ:0.89;95%CI,0.68~0.96;P<.001)和视网膜敏感度(ρ,-0.88;95%CI,-0.96至0.59;P<.001)。
■在这项横断面研究中,在疾病的共济失调前期发现了视网膜异常。大多数携带者表现为视锥细胞营养不良和保留的视杆功能。外核层厚度与SARA评分和血浆NfL水平相关,表明核层厚度是疾病严重程度的生物标志物。这些发现有助于了解SCA7相关视网膜营养不良的动态,并可能有助于为未来的治疗干预监测和临床试验奠定基础。
■ClinicalTrials.gov标识符:NCT04288128。
UNASSIGNED: Reliable biomarkers with diagnostic and prognostic values are needed for upcoming gene therapy trials for spinocerebellar ataxias.
UNASSIGNED: To identify ophthalmological biomarkers in a sample of spinocerebellar ataxia type 7 (SCA7) carriers.
UNASSIGNED: This article presents baseline data from a cross-sectional natural history study conducted in Paris, France, reference centers for rare diseases from May 2020 to April 2021. Data were analyzed from September to December 2022. Fifteen adult ATXN7 pathogenic expansion carriers (9 with preataxia and 6 with ataxia) were included, all with a Scale for the Assessment and Rating of Ataxia (SARA) score of 15 of 40 or lower. Patients were recruited at the Paris Brain Institute, and all contacted patients accepted to participate in the study.
UNASSIGNED: Three visits (baseline, 6 months, and 12 months) were planned, including neurological examination (SARA and Composite Cerebellar Functional Severity Score), ophthalmological examination (best-corrected visual acuity, microperimetry, full-field electroretinogram, optical coherence tomography, and fundus autofluorescence imaging), and neurofilament light chain (NfL) measurements. Here we report the baseline ophthalmic data from the cohort and determine whether there is a correlation between disease scores and ophthalmic results.
UNASSIGNED: Among the 15 included SCA7 carriers (median [range] age, 38 [18-60] years; 8 women and 7 men), 12 displayed cone or cone-rod dystrophy, with the number of CAG repeats correlating with disease severity (ρ, 0.73, 95% CI, 0.34 to 0.90; P < .001). Two patients with cone-rod dystrophy exhibited higher repeat numbers and greater ataxia scores (median [range] SARA score, 9 [7-15]) compared to those with only cone dystrophy (median [range] SARA score, 2 [0-5]). A correlation emerged for outer nuclear layer thickness with SARA score (ρ, -0.88; 95% CI, -0.96 to -0.59; P < .001) and NfL levels (ρ, -0.87; 95% CI, -0.86 to 0.96; P < .001). Moreover, ataxia severity was correlated with visual acuity (ρ: 0.89; 95% CI, 0.68 to 0.96; P < .001) and retinal sensitivity (ρ, -0.88; 95% CI, -0.96 to 0.59; P < .001).
UNASSIGNED: In this cross-sectional study, retinal abnormalities were found at preataxic stages of the disease. Most of the carriers presented with cone dystrophy and preserved rod function. The outer nuclear layer thickness correlated with SARA score and plasma NfL levels suggesting nuclear layer thickness to be a biomarker of disease severity. These findings contribute to understanding the dynamics of SCA7-related retinal dystrophy and may help lay the groundwork for future therapeutic intervention monitoring and clinical trials.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT04288128.