Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer’s disease pathophysiology

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 19, 2024

ABSTRACT INTRODUCTION Semorinemab, an anti-tau monoclonal antibody, was evaluated in two Phase II trials as a disease-modifying treatment for Alzheimer’s disease (AD). Plasma and cerebrospinal fluid (CSF) samples were collected from trial participants to evaluate the pharmacodynamic effects of semorinemab elucidate its mechanism action. METHODS Qualified immunoassays used measure plasma CSF biomarkers tau, amyloidosis, glial activity, neuroinflammation, synaptic function, neurodegeneration enrolled Tauriel ( NCT03289143 ) Lauriet NCT03828747 prodromal-to-mild (P2M) mild-to-moderate (M2M) AD. RESULTS Significant increases phosphorylated Tau 181 (pTau181) Chitinase-3-like protein 1 (YKL-40) followed administration both studies. In study, fibrillary (GFAP) levels rose progressively over study period placebo group, but remained stable time with semorinemab. contrast, this not observed study. Semorinemab had no consistent impact on other AD pathophysiology that evaluated. DISCUSSION engages stabilizes pTau181 manner previously reported data [1,2], do decrease after prolonged drug exposure. Increases YKL-40 suggest may stimulate microglia activation, while stabilization GFAP indicate moderate reactive gliosis M2M

Language: Английский

Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer's disease pathophysiology

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Semorinemab, 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.

Language: Английский