Contemporary Approaches in Drugs Discovery for Alzheimer's Disease Treatment.
Alzheimer's disease (AD) is characterized by a chronic and progressive neurodegenerative process resulting from the intracellular and extracellular accumulation of fibrillary proteins: beta-amyloid and hyperphosphorylated Tau. Overaccumulation of these aggregates leads to synaptic dysfunction and subsequent neuronal loss. The precise molecular mechanisms of AD are still not fully understood but it is clear that AD is a multifactorial disorder and that advanced age is the main risk factor. Over the last decade more than 50 drug candidates have successfully early phases clinical trials, but failed to reach the market. Here, we summarize data on "anti-Alzheimer's" agents currently in clinical trials based on available information in the Thomson Reuters «Integrity» database as well as public websites www.clinicaltrials.gov and Alzforum.org. We outline major trends in AD drug discovery: (1) compounds with the disease-modifying properties that could potentially slow the development of structural and functional abnormalities in the CNS providing sustainable improvements of cognitive functions, which persist even after drug withdrawal. (2) Focused design of multitargeted drugs acting on multiple molecular targets involved in the pathogenesis of the disease. (3) Finally, the repositioning of old drugs to fit new "anti-Alzheimer's" application offering a very attractive approach to facilitate successful completion of clinical trials.