For full story and links, go to:http://www.alzforum.org/new/detail.asp?id=2327
Clinical Trials Present a Mixed Picture"The failed amyloid drug/vaccine studies, although not definitive, were some of the most galvanizing and concerning findings related to AD in 2009," according to an ARF Advisor. Will ApoE genotype help predict response to therapy? Other approaches show promise, including an α7 nicotinic acetylcholine receptor (nAChR) agonist EVP-6124 and Dimebon.
Phase 2 Trial Launching for Prodromal ADBristol-Myers Squibb announced that it is recruiting for a 75-center Phase 2 trial of their new γ-secretase inhibitor, BMS-708163, in what that company calls “prodromal AD.”
ADNI Reaping FruitPublication of ADNI data is enabling different imaging, CSF modalities, and neuropsychological tests to be compared in terms of power to detect treatment effects in AD and MCI clinical trials.
Genomewide Association Studies Net Three New GenesThe two largest genomewide association studies of sporadic Alzheimer disease performed to date (Harold et al. and Williams et al.) fingered three new risk-factor genes—clusterin, CR1, PICALM. The most notable achievement of these studies lies in "the effort to collate data sets in support of larger samples, setting the trend we expect to see in the future," said an ARF Advisor.
Growing Emphasis on Presymptomatic DetectionCSF biomarker and imaging studies pointed toward the possibility of detecting prodromal AD. A study from Washington University showing that Aβ dynamics are regulated by orexin and sleep-wake cycle "adds a new perspective to the use of CSF Aβ as a diagnostic marker, as the reference values may have to be adjusted to the sampling timepoints," according to an ARF Advisor.
γ-Secretase ProgressProgress was made on elucidating the structure of γ-secretase. The paper by Serneels et al. described the role of the different Aph1 subtypes in the production of Aβ and in Notch-related toxicities. "With increasing numbers of failed clinical trials for γ-secretase inhibitors, this was especially important in (hopefully) injecting some renewed faith in γ-secretase as a viable target for AD drug development," an ARF Advisor opined.
Insights Into Synaptic Plasticity, Cognition, and Role of Aβ"The topic of synapses, β-amyloid, and synaptic/cognitive activity in AD continued to be a hot topic in the past year, with imaging and biological studies providing both new insights and questions," according to an ARF Advisor.
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