"The results from the Phase II CAD106 trial, which was completed in February 2013, are yet to be reported. Another ongoing active Phase II immunization trial, being conducted by Janssen and Pfizer, is ACC-001, which uses the same Ab(1–6) fragment coupled to a carrier protein and the surfaceactive saponin adjuvant QS-21 (Ryan and Grundman, 2009). Further, Affiris AG together with GlaxoSmithKline (GSK) has utilized AFFITOME(R) technology to generate synthetic antigenic peptides called mimotopes to target the unmodified Ab N terminus in their AD02 trials (Schneeberger et al., 2009). "
"Currently, several second-generation active Aβ vaccines are being tested in clinical trials (http://www.clinicaltrials.gov). Janssen and Pfizer are conducting Phase II studies to monitor the effects of their Aβ short N-terminus peptide-conjugate vaccine called ACC-001, formulated in the adjuvant QS-21 . Last year, Novartis Pharmaceuticals reported Phase I data for their active Aβ vaccine, CAD106, which consists of multiple copies of Aβ1-6 on QB virus-like particles with or without adjuvant . "
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease (AD) is the most common form of dementia, afflicting more than 30 million people worldwide. Currently, there is no cure or way to prevent this devastating disease. Extracellular plaques, containing various forms of amyloid-beta protein (Abeta), and intracellular neurofibrillary tangles (NFTs), composed of hyper-phosphorylated tau protein, are two major pathological hallmarks of the AD brain. Aggregation, deposition, and N-terminal modification of Abeta protein and tau phosphorylation and aggregation are thought to precede the onset of cognitive decline, which is better correlated with tangle formation and neuron loss. Active and passive vaccines against various forms of Abeta have shown promise in pre-clinical animal models. However, translating these results safely and effectively into humans has been challenging. Recent clinical trials showed little or no cognitive efficacy, possibly due to the fact that the aforementioned neurodegenerative processes most likely pre-existed in the patients well before the start of immunotherapy. Efforts are now underway to treat individuals at risk for AD prior to or in the earliest stages of cognitive decline with the hope of preventing or delaying the onset of the disease. In addition, efforts to immunize against tau and other AD-related targets are underway.
"Another strategy developed by Elan and Wyeth was the administration of ACC-001, an Aβ fragment attached to a carrier protein intended to help induce antibody generation. In phase I trials with ACC-001, an acute dose was found to be well tolerated and was shown to cross the BBB to increase clearance of Aβ from the CNS (Ryan and Grundman 2009). Recruitment for multiple phase II trials is currently ongoing. "
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease (AD) is the most prevalent form of dementia, affecting an estimated 4.8 million people in North America. For the past decade, the amyloid cascade hypothesis has dominated the field of AD research. This theory posits that the deposition of amyloid-beta protein (Abeta) in the brain is the key pathologic event in AD, which induces a series of neuropathological changes that manifest as cognitive decline and eventual dementia. Based on this theory, interventions that reduce Abeta burden in the brain would be expected to alleviate both the neuropathological changes and dementia, which characterize AD. Several diverse pharmacological strategies have been developed to accomplish this. These include inhibiting the formation of Abeta, preventing the aggregation of Abeta into insoluble aggregates, preventing the entry of Abeta into the brain from the periphery and enhancing the clearance of Abeta from the central nervous system. To date, no amyloid-modifying therapy has yet been successful in phase 3 clinical trials; however, several trials are currently underway. This article provides a review of the status of amyloid-modifying therapies and the implications for the amyloid cascade hypothesis.
Age 09/2010; 32(3):365-84. DOI:10.1007/s11357-010-9142-z · 3.45 Impact Factor
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