Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study

Winblad, Bengt; Andreasen, Niels; Minthon, Lennart; Floesser, Annette; Imbert, Georges; Dumortier, Thomas; Maguire, R. Paul; Blennow, Kaj; Lundmark, Joens; Staufenbiel, Matthias; Orgogozo, Jean‐Marc; Graf, Ana

doi:10.1016/s1474-4422(12)70140-0

Cited by 257 publications

(184 citation statements)

References 29 publications

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“…Some progress is being made in developing vaccines which modulate the course of diabetes and hypertension [42]. Vaccination against addiction, including smoking, is also feasible, although very high antibody concentrations are required to achieve an effect [43], and there are early results suggesting that vaccination against Alzheimer's disease might slow the progress of this condition [44]. In the coming decades, vaccination is likely to expand its scope beyond prevention of the common infections of childhood which has been its main success so far.…”

Section: The Long-term Future Of Vaccinationmentioning

confidence: 99%

The contribution of vaccination to global health: past, present and future

Greenwood

2014

Phil. Trans. R. Soc. B

690

516

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Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.

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Section: The Long-term Future Of Vaccinationmentioning

confidence: 99%

The contribution of vaccination to global health: past, present and future

Greenwood

2014

Phil. Trans. R. Soc. B

690

516

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“…The distinctive features of CSF, together with the low incidence of complications after lumbar puncture [62] have supported the introduction of lumbar puncture and analyses of CSF biomarkers into routine clinical practice in some centers [63,64]. CSF biomarkers are also increasingly used in clinical drug trials, both for enrichment of the target population at inclusion and to evaluate the biochemical effects of treatment [65][66][67].…”

Section: Cerebrospinal Fluid Biomarkersmentioning

confidence: 99%

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Hampel

Lista

Teipel

et al. 2014

Biochemical Pharmacology

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102

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Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD

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“…An over-exuberant T cell response appears to have been responsible for the meningoencephalitis that was observed in patients [98,99]. New trials have therefore focused on active [100], or passive vaccination that does not stimulate a T cell response [101]. Two phase III trials using passive immunization against Aβ did not meet their primary endpoints, although Solanezumab did show a small but significant reduction of cognitive decline in those with mild dementia after pooling data from two clinical trials [102], and based on this it is being carried forward to Phase III studies.…”

Section: Extracellular Clearance Degradation and Prevention Of Uptamentioning

confidence: 99%

Prion-Like Propagation of Protein Aggregation and Related Therapeutic Strategies

Kaufman

Diamond

2013

Neurotherapeutics

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Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study

Cited by 257 publications

References 29 publications

The contribution of vaccination to global health: past, present and future

The contribution of vaccination to global health: past, present and future

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Prion-Like Propagation of Protein Aggregation and Related Therapeutic Strategies

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