Title : The main trends in the developing novel therapeutics for alzheimer’s disease treatment
Abstract:
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. Over accumulation 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 passed phase II clinical trials, but none have passed phase III. Here, we summarize data on current “anti-Alzheimer’s” agents currently in clinical trials based on findings available in the Thomson Reuters «Integrity» database, on the public website www.clinicaltrials.gov, and on database of the website Alzforum.org. As a result, it was possible to outline some major trends in AD drug discovery: 1) the development of compounds acting on the main stages of the pathogenesis of the disease – the so-called “disease-modifying agents”. These drugs 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 for new (“anti-Alzheimer’s”) application, offers a very attractive approach to facilitate the completion of clinical trials [Bachurin S. et al., Med.Res.Rev.,(2017). 37(5):1186-1225].
