Alzheimer病の病態修飾療法の現在と未来

抄録

Alzheimer disease (AD) is a major public health challenge in aging societies, causing cognitive decline and impacting daily life. It affects over 55 million people worldwide, with numbers expected to rise to 139 million by 2050. Traditional treatments like Donepezil and Memantine focus on symptom alleviation but fail to alter disease progression. New disease–modifying therapies (DMTs) aim to slow or halt the disease progression by targeting its pathology. AD's pathology includes the aggregation of amyloid–beta (Aβ) plaques and tau proteins in the brain. These are key targets for DMT development. DMTs aim to enable longer independence for patients while reducing caregiving burdens and healthcare costs. Recent drugs, Lecanemab and Donanemab, have shown effectiveness in Phase 3 trials in reducing Aβ plaques and slowing disease progression by about 5.3–5.4 months over 18 months of treatment. Both drugs have associated side effects like ARIA (amyloid–related imaging abnormalities), which require careful management. Efforts are expanding into therapies targeting tau proteins, which are directly linked to AD symptoms. Promising developments include anti–tau antibodies and antisense oligonucleotides (ASOs) that reduce tau protein production and accumulation. Future developments focus on reducing side effects, enhancing effectiveness, improving patient convenience (e.g., subcutaneous administration), and exploring combination therapies. However, challenges such as competition with approved drugs and the exclusion of combination trials might complicate progress. The evolution of DMTs marks significant progress in AD treatment. Continued innovation is crucial for achieving safer and more effective therapies while navigating emerging challenges.