INTRODUCTIONSemorinemab, an anti‐tau monoclonal antibody, was assessed in two Phase II trials for Alzheimer's disease (AD). Plasma and cerebrospinal fluid (CSF) biomarkers provided insights into the drug's potential mechanism of action.METHODSQualified assays were used to measure biomarkers of tau, amyloidosis, glial activity, neuroinflammation, synaptic function, and neurodegeneration from participant samples in Tauriel (NCT03289143) and Lauriet (NCT03828747) Phase II trials.RESULTSPlasma phosphorylated Tau 181 (pTau181) and CSF chitinase‐3‐like protein 1 (YKL‐40) increased following semorinemab treatment in both studies. In Lauriet, increasing plasma glial fibrillary protein (GFAP) concentrations stabilized with semorinemab, while this was not observed in Tauriel. Other AD pathophysiology biomarkers showed no consistent response to semorinemab.DISCUSSIONIncreases in CSF YKL‐40 suggest that semorinemab may stimulate microglia activation in the presence of AD‐associated Tau pathology, but not in healthy controls. Stabilization of plasma GFAP in Lauriet indicates a possible impact on reactive gliosis in mild‐to‐moderate AD.Trial Registration: Tauriel ClinicalTrials.gov Identifier: NCT03289143. Lauriet ClinicalTrials.gov Identifier: NCT03828747. Phase 1 ClinicalTrials.gov Identifier: NCT02820896.Highlights AD pathophysiology biomarkers were measured to assess the mechanism of action. Semorinemab increased CSF YKL‐40 in participants with AD but not in healthy controls. Semorinemab possibly stabilized plasma GFAP in the Lauriet trial. Semorinemab treatment may activate microglia and moderate reactive gliosis.

中文翻译：

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semorinemab 对阿尔茨海默病病理生理学血浆和 CSF 生物标志物的药效学影响


引言 semorineab 是一种抗 tau 单克隆抗体，在阿尔茨海默病 （AD） 的两项 II 期试验中进行了评估。血浆和脑脊液 （CSF） 生物标志物为该药物的潜在作用机制提供了见解。方法在 Tauriel （NCT03289143） 和 Lauriet （NCT03828747） II 期试验中，使用定量测定法测量参与者样本的 tau 、淀粉样变性、神经胶质活性、神经炎症、突触功能和神经退行性变的生物标志物。结果在两项研究中，semorinemab 治疗后 pLasma 磷酸化 Tau 181 （pTau181） 和 CSF 几丁质酶-3-样蛋白 1 （YKL-40） 增加。在 Lauriet 中，血浆神经胶质纤维蛋白 （GFAP） 浓度的增加用 semorinemab 稳定下来，而在 Tauriel 中未观察到这种情况。其他 AD 病理生理学生物标志物显示对 semorinemab 没有一致的反应。讨论CSF YKL-40 的增加表明，semorinemab 可能在存在 AD 相关 Tau 病理的情况下刺激小胶质细胞活化，但在健康对照中则不然。Lauriet 血浆 GFAP 的稳定表明可能对轻度至中度 AD 的反应性神经胶质增生产生影响。Trial Registration： Tauriel ClinicalTrials.gov 标识符： NCT03289143.Lauriet ClinicalTrials.gov 标识符： NCT03828747.Phase 1 ClinicalTrials.gov 标识符：NCT02820896。亮点 测量 AD 病理生理学生物标志物以评估作用机制。Semorinemab 增加了 AD 参与者的 CSF YKL-40，但在健康对照者中没有增加。Semorinemab 可能在 Lauriet 试验中稳定了血浆 GFAP。Semorinemab 治疗可能会激活小胶质细胞和中度反应性神经胶质增生。