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Drugs in Clinical Trials for Alzheimer's Disease: The Major Trends.
Med Res Rev 2017; 37(5):1186-1225MR

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. 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 passed phase II clinical trials, but none has 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: (i) 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 central nervous system providing sustainable improvements of cognitive functions, which persist even after drug withdrawal; (ii) 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.

Authors+Show Affiliations

Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severny proezd 1, Chernogolovka, Moscow region, 142432, Russia.Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severny proezd 1, Chernogolovka, Moscow region, 142432, Russia.Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severny proezd 1, Chernogolovka, Moscow region, 142432, Russia.

Pub Type(s)

Journal Article
Review
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28084618

Citation

Bachurin, Sergey O., et al. "Drugs in Clinical Trials for Alzheimer's Disease: the Major Trends." Medicinal Research Reviews, vol. 37, no. 5, 2017, pp. 1186-1225.
Bachurin SO, Bovina EV, Ustyugov AA. Drugs in Clinical Trials for Alzheimer's Disease: The Major Trends. Med Res Rev. 2017;37(5):1186-1225.
Bachurin, S. O., Bovina, E. V., & Ustyugov, A. A. (2017). Drugs in Clinical Trials for Alzheimer's Disease: The Major Trends. Medicinal Research Reviews, 37(5), pp. 1186-1225. doi:10.1002/med.21434.
Bachurin SO, Bovina EV, Ustyugov AA. Drugs in Clinical Trials for Alzheimer's Disease: the Major Trends. Med Res Rev. 2017;37(5):1186-1225. PubMed PMID: 28084618.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drugs in Clinical Trials for Alzheimer's Disease: The Major Trends. AU - Bachurin,Sergey O, AU - Bovina,Elena V, AU - Ustyugov,Aleksey A, Y1 - 2017/01/13/ PY - 2016/08/12/received PY - 2016/10/18/revised PY - 2016/11/24/accepted PY - 2017/1/14/pubmed PY - 2018/4/24/medline PY - 2017/1/14/entrez KW - AD treatment KW - Alzheimer's disease KW - Tauopathy KW - amyloid-beta KW - clinical trial KW - disease-modifying drugs KW - multitargeting compounds KW - neurodegenerative disease KW - proteinopathy KW - repositioning of old drugs SP - 1186 EP - 1225 JF - Medicinal research reviews JO - Med Res Rev VL - 37 IS - 5 N2 - 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 passed phase II clinical trials, but none has 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: (i) 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 central nervous system providing sustainable improvements of cognitive functions, which persist even after drug withdrawal; (ii) 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. SN - 1098-1128 UR - https://www.unboundmedicine.com/medline/citation/28084618/Drugs_in_Clinical_Trials_for_Alzheimer's_Disease:_The_Major_Trends_ L2 - https://doi.org/10.1002/med.21434 DB - PRIME DP - Unbound Medicine ER -