2025 年 42 巻 3 号 p. 270-276
Neurodegenerative diseases are characterized by the accumulation of multiple pathogenic proteins both inside and outside brain cells. These proteins include tau, amyloid, α–synuclein, and TAR DNA binding protein–43. Previously, progressive supranuclear palsy (PSP) was believed to involve only tau protein accumulation. Two clinical trials using anti–tau antibodies (tilavonemab and gosuranemab) were conducted to target the toxic effects of tau protein, particularly its extracellular form. However, these antibodies failed to demonstrate clinical effectiveness. This highlights the complexity of treating neurodegenerative diseases. Corticobasal syndrome (CBS) presents additional challenges, as half of the patients show tau protein accumulation. The underlying pathology can include multiple conditions like corticobasal degeneration, PSP, and Alzheimer disease, each with a unique tau protein accumulation pattern. This diversity complicates the development of disease–modifying therapies (DMTs). As patient age, the presence of mixed pathologies becomes more common, making it crucial to carefully select therapeutic targets for clinical trials. To increase the likelihood of success, researchers need to : 1. Identify patients in the early stages of disease, 2. Use cerebrospinal fluid biomarkers or advanced imaging techniques like positron emission tomography. While some promising clinical trial results have been reported, more precise patient selection based on comprehensive biomarker analysis remains essential for developing effective treatments for neurodegenerative diseases.
