Anthony O. Caggiano, MD, PhD, Cognition Therapeutics, Inc., 2500 Westchester Avenue, Purchase, NY 10577,
J Prev Alzheimers Dis. 2024;11(6):1809-1817. doi: 10.14283/jpad.2024.154.
CT1812 is a first-in-class, sigma-2 receptor ligand, that prevents and displaces binding of amyloid beta (Aβ) oligomers. Normalization of quantitative electroencephalography (qEEG) markers suggests that CT1812 protects synapses from Aβ oligomer toxicity.
Evaluate CT1812 impact on synaptic function using qEEG measurements.
Phase 2, randomized, double-blind, placebo-controlled, 4-week crossover study.
VU University Medical Center and Brain Research Center Amsterdam, The Netherlands.
Adults with mild or moderate Alzheimer's disease (AD).
A daily 300 mg dose of CT1812 or placebo for 4 weeks.
A resting-state, eyes closed qEEG assessment occurred on Day 1 and on Day 29 of Treatment Periods 1 and 2, and at follow-up. The primary endpoint was global relative theta power (4-8 Hz), along with secondary EEG measures including global alpha corrected Amplitude Envelope Correlation (AEC-c). Cognitive and functional assessments, fluid biomarkers, and safety and tolerability were assessed.
16 patients were randomized, and 15 completed. A non-significant (p=0.123) but consistent reduction occurred in global relative theta power and in relative theta power in frontal, temporal, parietal, occipital and central (p<0.006) brain regions with CT1812. A nominally significant (p=0.034) improvement was observed in global alpha AEC-c. Adverse events occurred in 11 patients with CT1812 and 6 with placebo - most commonly nausea, diarrhea, and procedural headache. No severe or serious AEs, deaths or discontinuations were reported.
CT1812 improved established EEG markers of spontaneous brain activity (spectral power, functional connectivity) in patients with mild-to-moderate AD, suggesting improved neuronal/synaptic function within a 4-week timespan.
CT1812 是一种首创的 sigma-2 受体配体，可防止和置换淀粉样β（Aβ）寡聚物的结合。定量脑电图（qEEG）标志物的正常化表明 CT1812 可保护突触免受 Aβ寡聚物毒性的影响。
使用 qEEG 测量评估 CT1812 对突触功能的影响。
2 期、随机、双盲、安慰剂对照、4 周交叉研究。
荷兰阿姆斯特丹 VU 大学医学中心和脑研究中心。
患有轻度或中度阿尔茨海默病（AD）的成年人。
每日服用 300mg CT1812 或安慰剂，持续 4 周。
在治疗期 1 和 2 的第 1 天和第 29 天以及随访时进行静息状态、闭眼 qEEG 评估。主要终点是全局相对θ功率（4-8Hz），以及次要 EEG 测量，包括全局α校正的振幅包络相关（AEC-c）。评估认知和功能评估、液体生物标志物以及安全性和耐受性。
16 名患者被随机分配，15 名患者完成了研究。CT1812 治疗组患者的全局相对θ功率和额叶、颞叶、顶叶、枕叶和中央（p<0.006）脑区的相对θ功率均呈非显著（p=0.123）但一致降低。全局α AEC-c 观察到名义上的显著改善（p=0.034）。CT1812 治疗组有 11 名患者出现不良反应，安慰剂组有 6 名患者出现不良反应 - 最常见的是恶心、腹泻和程序头痛。没有严重或严重的不良事件、死亡或停药报告。
CT1812 改善了轻度至中度 AD 患者已建立的脑电图自发性脑活动标志物（谱功率、功能连接），表明在 4 周的时间内改善了神经元/突触功能。
