ABSTRACT
Introduction
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.
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 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.
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 Aβ pathophysiological role in AD put this novel experimental combination regimen at substantial risk of failure.
Article highlights
Drugs directed against amyloid-β (Aβ), the purported initial cause of the Alzheimer’s disease (AD), have been pursued for at least 20 years without any significant clinical success.
Neuroinflammation is an early phenomenon of the AD pathophysiology process with microglia and astrocytes as key cellular drivers and regulators.
Several traditional anti-inflammatory drugs directed against neuroinflammatory processes identified in the AD brain have also failed, both as preventive and therapeutic interventions.
The timing of therapy could be crucial considering that non-steroidal anti-inflammatory drugs use may be beneficial if begun when the brain was still normal.
The beneficial effect of ALZTOP1 (cromolyn sodium plus ibuprofen) is thought to be an experimental combination treatment regimen for AD targeting Aβ and neuroinflammation.
Future research efforts must encompass such alternative approaches directed toward neuroinflammation and related conditions (obesity, diabetes, infection).
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose