Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy.
Expert Opin Investig Drugs. 2022 Aug;31(8):759-771. doi: 10.1080/13543784.2022.2095261. Epub 2022 Jun 29.
For Alzheimer's disease (AD) treatment, US FDA granted accelerated approval for aducanumab due to its amyloid-β (Aβ)-lowering effects, notwithstanding the reported poor correlation between amyloid plaque reduction and clinical change for this drug. The diversification of drug targets appears to be the future of the AD field and from this perspective, drugs modulating microglia dysfunction and combination treatment regimens offer some promise.
The aim of the present article was to provide a comprehensive review of ALZT-OP1 (cromolyn sodium plus ibuprofen), an experimental combination treatment regimen for AD, discussing their mechanisms of action targeting Aβ and neuroinflammation, examining the role of microglia in AD and offering our own insights on the role of present and alternative approaches directed toward neuroinflammation.
Enrolling high-risk participants with elevated brain amyloid could help to slow cognitive decline in secondary prevention trials during AD preclinical stages. Long-term follow-up indicated that non-steroidal anti-inflammatory drugs use begun when the brain was still normal may benefit these patients, suggesting that the timing of therapy could be crucial. However, previous clinical failures and the present incomplete understanding of the Aβ pathophysiological role in AD put this novel experimental combination regimen at substantial risk of failure.
对于阿尔茨海默病（AD）的治疗，美国食品药品监督管理局（FDA）因其具有降低淀粉样蛋白-β（Aβ）的作用而加速批准了 aducanumab 的使用，尽管该药物的淀粉样斑块减少与临床变化之间的相关性较差。药物靶点的多样化似乎是 AD 领域的未来，从这个角度来看，调节小胶质细胞功能障碍的药物和联合治疗方案有一定的前景。
本文的目的是全面回顾 ALZT-OP1（色甘酸钠加布洛芬），一种用于 AD 的实验性联合治疗方案，讨论其针对 Aβ和神经炎症的作用机制，研究小胶质细胞在 AD 中的作用，并对目前和针对神经炎症的替代方法提供我们自己的见解。
在 AD 临床前阶段，招募有较高脑内淀粉样蛋白的高危参与者可能有助于减缓二级预防试验中的认知能力下降。长期随访表明，在大脑仍正常时开始使用非甾体抗炎药可能对这些患者有益，这表明治疗时机可能至关重要。然而，先前的临床失败以及目前对 AD 中 Aβ 病理生理学作用的不完全了解，使这种新的实验性联合治疗方案面临着巨大的失败风险。
