O2‐05‐05: Results of the first‐in‐man study with the active Aβ Immunotherapy CAD106 in Alzheimer patients

Winblad, Bengt; Minthon, Lennart; Floesser, Annette; Imbert, Georges; Dumortier, Thomas; He, Yan-Ling; Maguire, Patrick D.; Karlsson, Malin; Östlund, Hanna; Lundmark, Joens; Orgogozo, Jean‐Marc; Graf, Ana; Andreasen, Niels

doi:10.1016/j.jalz.2009.05.356

Cited by 30 publications

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“…The discovery of such disease-modifying therapies has in part relied in preclinical testing in validated animal models [23]. For example, initial studies in AβPP Tg mice that demonstrated that immunotherapy promotes clearance of Aβ from the central nervous system have resulted in a number of such anti-Aβ antibodies going into human clinical trials [24–31]. Subsequent post-mortem examination in a small group of AD cases and more recently PET studies with Pittsburgh compound B showed that in vaccinated patients the levels of Aβ deposits were decreased [32] attesting to the value of some of the AβPP Tg models.…”

Section: Introductionmentioning

confidence: 99%

A Longitudinal Study of Behavioral Deficits in an AβPP Transgenic Mouse Model of Alzheimer's Disease

Havas¹,

Hutter‐Paier²,

Ubhi

et al. 2011

JAD

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Elucidating the age-dependent alterations in transgenic (Tg) mice overexpressing amyloid-β protein precursor (AβPP) is important for understanding the pathogenesis of Alzheimer’s disease (AD) and designing experimental therapies. Cross-studies have previously characterized some time-dependent behavioral and pathological alterations in AβPP Tg mice, however, a more comprehensive longitudinal study is needed to fully examine the progressive nature of behavioral deficits in these mice. In order to better understand the age- and gender-dependent progression of behavioral alterations, we performed a longitudinal study wherein Tg mice overexpressing human AβPP751 with the London (V717I) and Swedish (K670M/N671L) mutations under the regulatory control of the neuron specific murine (m)Thy-1 promoter (mThy1-hAβPP751) were behaviorally analyzed at 3 months and then re-tested at 6 and 9 months of age. The results show that there was an age-associated impairment in learning in the water maze task and habituation in the hole-board task. Motor coordination of the mThy1-hAβPP751 Tg mice was well-preserved throughout the investigated life span however, gender-specific deficits were observed in spontaneous activity and thigmotaxis. Neuropathologically, mThy1-hAβPP751 Tg mice displayed a progressive increase in the number of Aβ plaques and mean plaque size in the cortex and hippocampus from 3 to 6 and from 6 to 9 months of age. Taken together, these results indicate that the mThy1-hAβPP751 Tg mice model AD from the early onset of the disease through to later stages, allowing them to be utilized at numerous points during the timeline for drug test designs.

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Section: Introductionmentioning

confidence: 99%

A Longitudinal Study of Behavioral Deficits in an AβPP Transgenic Mouse Model of Alzheimer's Disease

Havas¹,

Hutter‐Paier²,

Ubhi

et al. 2011

JAD

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“…Three doses of 50 µg or 150 µg of the vaccine resulted in a generally favorable safety profile and anti-Ab antibody responses in 16 of 24 patients immunized at the 50 µg dose and 18 of 22 patients at the 150 µg dose. 55 No differences were observed in clinical assessment, Ab levels in the CSF or brain volume between the vaccinated groups and the placebo controls. Phase 2 trials of this vaccine are ongoing and are expected to be completed in June 2011.…”

Section: Vlps As Platforms For Antigenic Displaymentioning

confidence: 88%

Virus-like particle based vaccines for Alzheimer disease

Chackerian¹

2010

Human Vaccines

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“…Subsequent clinical trials have included active immunization with CAD-106 (Novartis), a peptide vaccine that contains a short N-terminal fragment of Aβ which reportedly does not induce the T-cell response observed with AN-1792 (Lemere and Masliah, 2010). Results from this trail report no significant differences between CSF Aβ levels and MRI whole brain volumes between treated and placebo patients (Winblad, et al, 2009). A number of clinical trials of active immunization are still ongoing, these include the Merck V950 antibody, a peptide also based on the N-terminal region of Aβ and the Elan/Wyeth Pharmaceutical Aβ immuno-conjugate AAC-001, where a fragment of Aβ is attached to a carrier protein, though this trial was suspended in 2008 when a patient developed skin lesions it is now recruiting again for a Phase II trial.…”

Section: The Challenge Of Alzheimer Disease Therapeutics - a Role Formentioning

confidence: 99%

Recent advances in the development of immunotherapies for tauopathies

Ubhi

Masliah

2011

Experimental Neurology

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The use of immunotherapy for Alzheimer’s Disease (AD) has traditionally focused on the amyloid-β (Aβ) peptide and has shown great potential in both animal and human studies. However an emerging body of work has begun to concentrate on tau and to develop immunization protocols designed to decrease tau pathology in AD and other tauopathies. This commentary will discuss the use of immunotherapy for AD, focusing on tau immunotherapy in the context of recent reports on the use of tau phospho-peptides in transgenic models of tau pathology.

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O2‐05‐05: Results of the first‐in‐man study with the active Aβ Immunotherapy CAD106 in Alzheimer patients

Cited by 30 publications

References 0 publications

A Longitudinal Study of Behavioral Deficits in an AβPP Transgenic Mouse Model of Alzheimer's Disease

A Longitudinal Study of Behavioral Deficits in an AβPP Transgenic Mouse Model of Alzheimer's Disease

Virus-like particle based vaccines for Alzheimer disease

Recent advances in the development of immunotherapies for tauopathies

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