Osaka Hitoshi, Nishida Keiichiro, Kanazawa Tetsufumi
Department of Neuropsychiatry Osaka Medical and Pharmaceutical University Takatsuki Osaka Japan.
PCN Rep. 2024 Mar 20;3(1):e185. doi: 10.1002/pcn5.185. eCollection 2024 Mar.
This review focuses on the development of therapeutic interventions for Alzheimer's dementia. While established treatments targeted acetylcholine and NMDA receptors, there is a growing demand for innovative therapies as the aging population increases. The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments. Specifically, it covers seven principal drugs in Phase III trials, detailing their mechanisms of action, clinical trial specifics in the United States and Japan, and the current status of regulatory applications. The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease-modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients.
本综述聚焦于阿尔茨海默病痴呆症治疗干预措施的发展。虽然已有的治疗方法针对乙酰胆碱和N-甲基-D-天冬氨酸（NMDA）受体，但随着老龄化人口的增加，对创新疗法的需求也在不断增长。本文强调了美国食品药品监督管理局对阿杜卡奴单抗（Aduhelm）和仑卡奈单抗（Leqembi）的批准，着重介绍了新治疗方法的研发进展。具体而言，它涵盖了处于III期试验的七种主要药物，详细阐述了它们的作用机制、在美国和日本的临床试验细节以及监管申请的现状。该综述聚焦于淀粉样蛋白清除（多那奈单抗）、tau蛋白缓解（E2814）、药物重新定位（司美格鲁肽、GV1001）以及疾病修饰小分子（福斯戈尼美顿、肼屈嗪、马西替尼）。然而，在III期试验中未成功的甘特奈单抗和索拉奈单抗未被涵盖。虽然未来的批准情况仍不确定，但我们希望这些药物能为潜在的痴呆症患者带来有益的治疗效果。
