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.
Keywords: Alzheimer’s disease, disease-modifying drug, clinical trials, β-amyloid.
Current Topics in Medicinal Chemistry
Title:Clinical Pharmacology of Novel Anti-Alzheimer Disease Modifying Medications
Volume: 13 Issue: 15
Author(s): Filippo Caraci, Paolo Bosco, Gian Marco Leggio, Michele Malaguarnera, Filippo Drago, Claudio Bucolo and Salvatore Salomone
Affiliation:
Keywords: Alzheimer’s disease, disease-modifying drug, clinical trials, β-amyloid.
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.
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Caraci Filippo, Bosco Paolo, Leggio Marco Gian, Malaguarnera Michele, Drago Filippo, Bucolo Claudio and Salomone Salvatore, Clinical Pharmacology of Novel Anti-Alzheimer Disease Modifying Medications, Current Topics in Medicinal Chemistry 2013; 13 (15) . https://dx.doi.org/10.2174/15680266113139990141
DOI https://dx.doi.org/10.2174/15680266113139990141 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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