Clinical pharmacology of novel anti-Alzheimer disease modifying medications

Filippo Caraci, Paolo Bosco, Gian Marco Leggio, Michele Malaguarnera, Filippo Drago, Claudio Bucolo, Salvatore Salomone

Research output: Contribution to journalArticlepeer-review

Abstract

In recent years, efforts have been directed to develop "disease-modifying" medications to treat Alzheimer's disease (AD), able to halt or slow the pathological process. Because the earlier the treatment starts, the greater is the possibility of efficacy, it is important to set up biomarkers for early diagnosis of functional brain abnormalities, before the clinical manifestation of the overt disease. Up to now, strategies to develop disease-modifying drugs have mainly targeted β amyloid (Aβ, accumulation, aggregation, clearance) and/or tau protein (phosphorylation and aggregation). Active and passive immunotherapy is the main strategy aimed at increasing Aβ clearance. Unfortunately several candidate diseasemodifying drugs have failed in phase III clinical trials conducted in mild to moderate AD. More recently, in phase III studies, bapineuzumab has been discontinued because it did not prove clinically effective (despite its significant effect on biomarkers), while solaneuzumab has been found effective in slowing AD progression. Several methological problems have been recently pointed out to explain the lack of clinical efficacy of novel disease-modifying drug-treatments; moreover, new insights in pathophysiology of AD give the premise to develop novel drug targeting. Clinical trials recently completed and/or still ongoing are discussed in the present review.

Original languageEnglish
Pages (from-to)1853-1863
Number of pages11
JournalCurrent Topics in Medicinal Chemistry
Volume13
Issue number15
Publication statusPublished - 2013

Keywords

  • β-amyloid
  • Alzheimer's disease
  • Clinical trials
  • Disease-modifying drug

ASJC Scopus subject areas

  • Drug Discovery

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