Category: Parkinsonism, Atypical: PSP, CBD
Objective: The purpose of this study is to examine the modification of tau pathology in brain regions of a patient with progressive supranuclear palsy (PSP) who was treated with a monoclonal antibody against tau.
Background: PSP is a neurodegenerative disease characterized by motor and behavioral symptoms, including vertical supranuclear gaze palsy and postural instability. Although some PSP-parkinsonism patients have received a limited benefit from levodopa therapy, there is currently no effective treatment for PSP. A novel tau-directed monoclonal antibody, Tilavonemab, was developed, and AbbVie started a clinical trial for PSP patients.
Method: Neuropathological examination of a PSP patient, who had been enrolled in a phase 2 trial and received an active drug (2000 mg/infusion of Tilavonemab), was performed. Other three PSP patients without administration of a monoclonal tau antibody were also examined. For immunohistochemistry, the primary antibodies used were mouse monoclonal antibodies against human phosphorylated tau (p-tau), 4-repeat isoform tau, and CD68.
Results: Neuropathological examination of all PSP cases demonstrated widespread deposits of p-tau in the neurofibrillary tangles, neuropil threads, tufted astrocytes, and coiled bodies mainly in the dentate nucleus of the cerebellum, substantia nigra, midbrain tegmentum, subthalamic nuclei, globus pallidus, putamen, and precentral gyrus. In the patient treated with Tilavonemab, accumulation of p-tau was also found to accumulate in Betz cells, Purkinje cells, and pencil fibers in the basal ganglia. Moreover, phagocytosis of abnormal tau by activated microglia/macrophages was observed in the substantia nigra.
Conclusion: Our study suggests that a tau-directed monoclonal antibody could alter the tau pathology of PSP and might promote microglia/macrophage-mediated phagocytosis.
To cite this abstract in AMA style:
G. Beck, R. Yamashita, Y. Yonenobu, K. Ikenaka, S. Murayama, H. Mochizuki. A tau-directed monoclonal antibody could alter the tau pathology of progressive supranuclear palsy [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/a-tau-directed-monoclonal-antibody-could-alter-the-tau-pathology-of-progressive-supranuclear-palsy/. Accessed June 15, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-tau-directed-monoclonal-antibody-could-alter-the-tau-pathology-of-progressive-supranuclear-palsy/