Panza Francesco, Seripa Davide, Solfrizzi Vincenzo, Imbimbo Bruno P, Lozupone Madia, Leo Antonio, Sardone Rodolfo, Gagliardi Gaetano, Lofano Lucia, Creanza Bianca C, Bisceglia Paola, Daniele Antonio, Bellomo Antonello, Greco Antonio, Logroscino Giancarlo
a Unit of Neurodegenerative Disease, Department of Basic Medicine Sciences, Neuroscience, and Sense Organs , University of Bari 'Aldo Moro' , Bari , Italy.
b Unit of Neurodegenerative Disease, Department of Clinical Research in Neurology , University of Bari 'Aldo Moro' at 'Pia Fondazione Card. G. Panico' , Lecce , Italy.
Expert Opin Emerg Drugs. 2016 Dec;21(4):377-391. doi: 10.1080/14728214.2016.1241232. Epub 2016 Oct 6.
Currently available drugs against Alzheimer's disease (AD) target cholinergic and glutamatergic neurotransmissions without affecting the underlying disease process. Putative disease-modifying drugs are in development and target β-amyloid (Aβ) peptide and tau protein, the principal neurophatological hallmarks of the disease. Areas covered: Phase III clinical studies of emerging anti-Aβ drugs for the treatment of AD were searched in US and EU clinical trial registries and in the medical literature until May 2016. Expert opinion: Drugs in Phase III clinical development for AD include one inhibitor of the β-secretase cleaving enzyme (BACE) (verubecestat), three anti-Aβ monoclonal antibodies (solanezumab, gantenerumab, and aducanumab), an inhibitor of receptor for advanced glycation end products (RAGE) (azeliragon) and the combination of cromolyn sodium and ibuprofen (ALZT-OP1). These drugs are mainly being tested in subjects during early phases of AD or in subjects at preclinical stage of familial AD or even in asymptomatic subjects at high risk of developing AD. The hope is to intervene in the disease process when it is not too late. However, previous clinical failures with anti-Aβ drugs and the lack of fully understanding of the pathophysiological role of Aβ in the development of AD, put the new drugs at substantial risk of failure.
目前可用的抗阿尔茨海默病（AD）药物作用于胆碱能和谷氨酸能神经传递，而不影响潜在的疾病进程。正在研发的潜在疾病修饰药物作用于β-淀粉样蛋白（Aβ）肽和tau蛋白，这是该疾病主要的神经病理学特征。涵盖领域：在美国和欧盟临床试验注册库以及医学文献中检索截至2016年5月新兴抗Aβ药物治疗AD的III期临床研究。专家观点：处于AD III期临床开发的药物包括一种β-分泌酶切割酶（BACE）抑制剂（verubecestat）、三种抗Aβ单克隆抗体（solanezumab、gantenerumab和aducanumab）、一种晚期糖基化终产物受体（RAGE）抑制剂（azeliragon）以及色甘酸钠和布洛芬的组合（ALZT-OP1）。这些药物主要在AD早期阶段的受试者、家族性AD临床前阶段的受试者甚至是有发展为AD高风险的无症状受试者中进行测试。希望在为时未晚时干预疾病进程。然而，此前抗Aβ药物的临床失败以及对Aβ在AD发展中病理生理作用的不完全理解，使这些新药面临巨大的失败风险。
