ALZT-OP1: an experimental combination regimen for the treatment of Alzheimer's disease

Introduction: For Alzheimer's disease (AD) treatment, US FDA granted accelerated approval for aducanumab due to its amyloid-beta (A beta)-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.Areas covered: 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 A beta 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.Expert opinion: 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 A beta pathophysiological role in AD put this novel experimental combination regimen at substantial risk of failure.