PDF(Pubmed)
Abstract：
We evaluated the efficacy and safety of 1-year treatment with nilotinib (Tasigna®) in patients with autosomal dominant spinocerebellar ataxia (ADSCA) and the factors associated with responsiveness. From an institutional cohort, patients with ADSCA who completed a 1-year treatment with nilotinib (150-300 mg/day) were included. Ataxia severity was assessed using the Scale for the Rating and Assessment of Ataxia (SARA), scores at baseline and 1, 3, 6, and 12 months. A subject was categorized \'responsive\' when the SARA score reduction at 12 M was > 0. Pretreatment serum proteomic analysis included subjects with the highest (n = 5) and lowest (n = 5) SARA score change at 12 months and five non-ataxia controls. Thirty-two subjects (18 [56.2%] females, median age 42 [30-49.5] years) were included. Although SARA score at 12 M did not significantly improve in overall population, 20 (62.5%) subjects were categorized as responsive. Serum proteomic analysis identified 4 differentially expressed proteins, leucine-rich alpha-2-glycoprotein (LRG1), vitamin-D binding protein (DBP), and C4b-binding protein (C4BP) beta and alpha chain, which are involved in the autophagy process. This preliminary data suggests that nilotinib might improve ataxia severity in some patients with ADSCA. Serum protein markers might be a clue to predict the response to nilotinib.Trial Registration Information: Effect of Nilotinib in Cerebellar Ataxia Patients (NCT03932669, date of submission 01/05/2019).
摘要：
我们评估了尼洛替尼（Tasigna®）治疗常染色体显性遗传性脊髓小脑共济失调（ADSCA）的疗效和安全性，以及与反应性相关的因素。从一个机构群体来看，纳入完成尼洛替尼(150~300mg/d)1年治疗的ADSCA患者.共济失调的严重程度采用共济失调评级和评估量表（SARA）进行评估，基线和1,3,6和12个月时的评分.当12M时SARA评分降低>0时,受试者被归类为“反应性”。治疗前血清蛋白质组分析包括在12个月时具有最高(n=5)和最低(n=5)SARA评分变化的受试者和五个非共济失调对照。32名受试者(18名[56.2%]名女性，包括中位年龄42[30-49.5]岁)。尽管12M时的SARA评分在总体人群中没有显着改善，20名（62.5%）受试者被归类为有反应的。血清蛋白质组学分析确定了4种差异表达的蛋白质，富含亮氨酸的α-2-糖蛋白（LRG1），维生素D结合蛋白（DBP），和C4b结合蛋白（C4BP）β和α链，参与自噬过程。这些初步数据表明，尼洛替尼可能会改善一些ADSCA患者的共济失调严重程度。血清蛋白标志物可能是预测尼洛替尼反应的线索。试验注册信息：尼洛替尼在小脑共济失调患者中的作用（NCT03932669，提交日期01/05/2019）。
