SLAS

Poster: A Novel Multifactorial Drug Candidate for Alzheimer's Disease: High-Throughput Screening, Identification and Efficacy Characterization

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Poster presentation at MipTec 2012
Winner of a SLAS Young Scientist Award.

Alexander Daschner and Kamran Honarnejad
German Centre for Neurodegenerative Diseases (DZNE) at Ludwig-Maximilians-Universität in Munich, Germany

Abstract

After more than 100 years of research on Alzheimer’s disease (AD) there is still no effective therapy available. The pathological hallmarks of the disease are extracellular Abeta plaques and intracellular neurofibrillary tangles consisting of hyperphosphorylated tau. Disruption of calcium homeostasis is an early pathological event in disease progression leading to those hallmarks. By screening 20,000 small molecules using a novel high-throughput-screen, we identified a new class of compounds which stabilize altered ER calcium homeostasis. On top of this effect our multi-functional lead structure is able to enhance mitochondrial function and lower Abeta protein levels at the same time. The most promising lead-structure analogue was also tested for toxicity and pharmacokinetic properties. It is well tolerable and penetrates the blood-brain-barrier. In contrast to other drug development approaches our lead structure shows beneficial effects at multiple pathophysiological aspects of Alzheimer’s disease.