Mahdavi Kennedy D, Jordan Sheldon E, Barrows Hannah R, Pravdic Maša, Habelhah Barshen, Evans Natalie E, Blades Robin B, Iovine Jessica J, Becerra Sergio A, Steiner Rachel A, Chang Marisa, Kesari Santosh, Bystritsky Alexander, O'Connor Ed, Gross Hyman, Pereles F Scott, Whitney Mike, Kuhn Taylor
Neurological Associates - The Interventional Group (KDM, MP, BH, NEE, RBB, JJI, RAS, MC), Santa Monica, CA; Department of Neurology (SEJ), University of California, Los Angeles; Neurological Associates of West Los Angeles (HRB, EOC), Santa Monica, CA; Synaptec Network (SAB), Santa Monica, CA; Pacific Neuroscience Institute (SK), Santa Monica, CA; Department of Psychiatry and Biobehavioral Sciences (AB, TK) University of California, Los Angeles; Department of Neurology (HG), University of Southern California, Los Angeles; and Rad Alliance, Inc. (FSP, MW), Los Angeles, CA.
Neurol Clin Pract. 2021 Jun;11(3):e294-e302. doi: 10.1212/CPJ.0000000000000918.
The pursuit of an effective therapeutic intervention for dementia has inspired interest in the class of medications known as tyrosine kinase inhibitors such as bosutinib.
Thirty-one patients with probable Alzheimer dementia or Parkinson spectrum disorder with dementia completed 12 months of bosutinib therapy and an additional 12 months of follow-up. The Clinical Dementia Rating scale (as estimated by the Quick Dementia Rating System [QDRS]) was the primary cognitive status outcome measure. Secondary outcome measures included the Repeatable Battery Assessment of Neuropsychological Status (RBANS) and the Montreal Cognitive Assessment. Cox regression methods were used to compare results with population-based estimates of cognitive decline.
The present article reports on cognitive outcomes obtained at 12 months for 31 participants and up to 24 months for a 16-participant subset. Safety and tolerability of bosutinib were confirmed among the study population (M = 73.7 years, SD = 14 years). Bosutinib was associated with less worsening in Clinical Dementia Rating (CDR) scores (hazard ratio = -0.62, < 0.001, 95% confidence interval [CI]: -1.02 to -0.30) and less decline in RBANS performance (hazard ratio = -3.42, < 0.001, 95% CI: -3.59 to -3.72) during the year of treatment than population-based estimates of decline. In the 24-month follow-up, wherein 16 patients were observed after 1 year postintervention, 31.2% of participants exhibited worsened CDR levels compared with their 12-month performances.
Results support an overall positive outcome after 1 year of bosutinib. Future studies should explore the relationship between tyrosine kinases and neurodegenerative pathology as well as related avenues of treatment.
寻求有效的痴呆治疗干预措施激发了人们对一类名为酪氨酸激酶抑制剂（如博舒替尼）药物的兴趣。
31例可能患有阿尔茨海默病痴呆或帕金森谱系障碍伴痴呆的患者完成了12个月的博舒替尼治疗及额外12个月的随访。临床痴呆评定量表（由快速痴呆评定系统[QDRS]评估）是主要的认知状态结局指标。次要结局指标包括可重复神经心理状态成套测验（RBANS）和蒙特利尔认知评估。采用Cox回归方法将结果与基于人群的认知衰退估计值进行比较。
本文报告了31名参与者在12个月时以及16名参与者亚组长达24个月时获得的认知结局。在研究人群（平均年龄M = 73.7岁，标准差SD = 14岁）中证实了博舒替尼的安全性和耐受性。与基于人群的衰退估计值相比，在治疗的一年中，博舒替尼与临床痴呆评定量表（CDR）评分恶化程度较低（风险比 = -0.62，P < 0.001，95%置信区间[CI]：-1.02至-0.30）以及RBANS表现下降较少（风险比 = -3.42，P < 0.001，95% CI：-3.59至-3.72）相关。在24个月的随访中，其中16名患者在干预后1年进行观察，31.2%的参与者与他们12个月时的表现相比，CDR水平恶化。
结果支持博舒替尼治疗1年后总体呈阳性结局。未来的研究应探索酪氨酸激酶与神经退行性病变之间的关系以及相关的治疗途径。
