Retracted: ‘Clinical trials in Alzheimer’s disease’: immunotherapy approaches

Abstract

J. Neurochem. (2012) 120 (Suppl. 1), 186–193. Abstract Recent advances in the understanding of Alzheimer’s disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β (Aβ) peptide represents an important molecular target for intervention in Alzheimer’s disease. Several types of Aβ peptide immunotherapy for Alzheimer’s disease are under investigation, direct immunization with synthetic intact Aβ42, active immunization involving the administration of synthetic fragments of Aβ peptide conjugated to a carrier protein and passive administration with monoclonal antibodies directed against Aβ peptide. Pre‐clinical studies showed that immunization against Aβ peptide can provide protection and reversal of the pathology of Alzheimer’s disease in animal models. Indeed, several adverse events have been described like meningoencephalitis with AN1792, vasogenic edema and microhemorrhages with bapineuzumab. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer’s disease, this clearance did not show significant cognitive effect for the moment. Currently, several Aβ peptide immunotherapy approaches are under investigation but also against tau pathology.

Developing Therapeutic Antibodies for Neurodegenerative Disease

“…Removing Amyloid Via Anti-Aβ Treatment Numerous reviews have addressed the immunotherapeutic approaches to target Aβ [4,34,[55][56][57]; thus, we will focus on the debate around the mechanism(s) of anti-Aβ action ( Fig. 2b) and the most recent clinical advances.…”

Comparison of Efficacy of Preventive and Therapeutic Vaccines Targeting the N Terminus of β-Amyloid in an Animal Model of Alzheimer’s Disease

“…[21][22][23] Because immunotherapeutic strategies displayed great promise in animal models of AD, a strong effort was made by the industry to inhibit generation of toxic Ab aggregates and remove soluble and aggregated Ab deposited in the brains of AD patients by both active and passive anti-Ab immunotherapy strategies. [24][25][26][27][28][29][30][31] Data from active vaccine trials indicate that, to be effective, anti-Ab therapeutic should induce high titers of anti-Ab antibodies without activation of autoreactive T cells. [31][32][33][34] On the other hand, published results from both active and passive Ab-immunotherapy suggest that it should be initiated early in the disease, probably before toxic forms of this peptide accumulate in the brain.…”

Amyloid-β Peptide-specific DARPins as a Novel Class of Potential Therapeutics for Alzheimer Disease

“…DARPin D23 at 50 nM was preincubated with a 50-fold molar excess of the peptide fragments A␤(Ϫ4 -6), A␤(Ϫ3-7), A␤(Ϫ2-8), A␤(Ϫ1-9), A␤(1-8), A␤(2-11), A␤ (3)(4)(5)(6)(7)(8)(9)(10)(11)(12), A␤(4 -13), A␤ (5)(6)(7)(8)(9)(10)(11)(12)(13)(14), A␤(6 -15) (peptides&elephants, Potsdam, Germany), A␤(1-11), A␤ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), A␤ (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)…”

“…To date, more than one dozen anti-amyloid immunotherapy clinical trials, testing both passive immunotherapy and active vaccination strategies, are currently underway for the treatment of AD (9).…”