The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-0604

  • © 1998-2025
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Bachurin S.O.

A review of drugs for treatment of Alzheimer’s disease in clinical trials: main trends

Authors:

Bachurin S.O.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(8): 77‑87

DOI: 10.17116/jnevro20161168177-87

Views: 7883

Downloaded: 202

Download PDF (RU)
Contact the author
Table of contents

To cite this article:

Bachurin SO. A review of drugs for treatment of Alzheimer’s disease in clinical trials: main trends. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(8):77‑87. (In Russ.)
https://doi.org/10.17116/jnevro20161168177-87

 
МСФ на ЯМ
Close metadata
Recommended articles:
Glymphatic dysfunction and sleep diso­rders: indi­rect effe­cts on Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4):7-12
Ginkgolide B: mechanisms of neurobiological effe­cts, prospects for use in the therapy of Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4):22-27
Comparative characteristics of neuropsychological and neurometabolic changes in patients with Alzheimer’s disease and vascular cognitive impairment. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4-2):17-24
Impairment of atte­ntion and executive functions in chro­nic cere­brovascular disease and Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4-2):25-32
Asse­ssment of the significance of dila­ted peri­vascular spaces and nocture arte­rial hype­rtension in the deve­lopment of Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;(4-2):33-40
Mole­cular Gene­tic Aspe­cts of Vari­cose Vein Disease: Modern Concepts. Journal of Venous Diso­rders. 2024;(1):48-53
Gene­tic factors in dege­nerative disc disease. Burdenko's Journal of Neurosurgery. 2024;(2):112-118
Pathogenetic, clinical-diagnostic and therapeutic aspe­cts of premenstrual syndrome. Russian Bulletin of Obstetrician-Gynecologist. 2024;(2):37-42
Morphological features of vaso­proliferative tumor of the retina. Russian Journal of Archive of Pathology. 2024;(2):42-50
Clinical and morphological asse­ssment of patients with adenomyosis: own data. Russian Journal of Human Reproduction. 2024;(2):130-135

Development of drugs for treatment of neurodegenerative diseases, including Alzheimer’s disease (AD), is thought to be a complicated problem of current medical chemistry. According to current concepts, AD is proteinopathy due to impairments in the metabolism of amyloid precursor protein and tau-protein that results in the pathological protein aggregation in the brain. The author describes about 130 compound used in clinical trials of AD in 2015 and presents major characteristics of their action. It has allowed to find the following trends in a search for drugs for AD: 1. Development of disease modifying drugs, 2. Drugs, which act on several molecular targets simultaneously, 3. Search for new possibilities of using known drugs (drug reposition).

Keywords:

Alzheimer’s disease
pathogenesis
β-amiloid
tau-protein
multitarget drugs

Authors:

Bachurin S.O.

List of references:

  1. Skripka-Serry J. The great neuro-pipeline «brain drain» (and why Big Pharma hasn’t given up on CNS disorders). Drug discovery World Fall. 2013;9-16. Available at: http://www.ddw-online.com/therapeutics/p216813-the-great-neuro-pipeline-brain-drain-(and-why-big-pharma-hasn-t-given-up-on-cns-disorders)-fall-13.html
  2. Cummings J, Morstorf T, Zhong K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimer’s Research Therapy. 2014;6:37.  doi: 10.1186/alzrt269
  3. Nussbaum JM, Seward ME, Bloom GS. Alzheimer disease: a tale of two prions. Prion. 2013;7(1):14-19.  doi: 10.4161/pri.22118
  4. Khlistunova I, Biernat J, Wang Y, Pickhardt M, von Bergen M, Gazova Z, Mandelkow E, Mandelkow E. Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs. J Biol Chem. 2006;281(2):1205-1214. doi: 10.1074/jbc.M507753200
  5. Carreiras MC, Mendes E, Perry MJ, Francisco AP, Marco-Contelles J. The multifactorial nature of Alzheimer's disease for developing potential therapeutics. Curr Top Med Chem. 2013;13(15):1745-1770. doi: 10.2174/15680266113139990135
  6. Nordberg A. Mechanisms behind the neuroprotective actions of cholinesterase inhibitors in Alzheimer disease. Alzheimer Dis Assoc Disord. 2006;20(2 suppl 1):12-18.  doi: 10.1097/01.wad.0000213804.59187.2d
  7. Chalmers KA, Wilcock GK, Vinters HV, Perry EK, Perry R, Ballard CG, Love S. Cholinesterase inhibitors may increase phosphorylated tau in Alzheimer's disease. J Neurol. 2009;256(5):717-720.  doi: 10.1007/s00415-009-5000-2
  8. Danysz W, Parsons CG. Alzheimer's disease, beta-amyloid, glutamate, NMDA receptors and memantine - searching for the connections. Br J Pharmacol. 2012;167(2):324-352.  doi: 10.1111/j.1476-5381.2012.02057.x
  9. Cohen C, Blanchard V, Debeir T et al. SAR228810: An antiprotofibrillar beta-amyloid antibody designed to reduce risk of amyloid-related imaging abnormalities (ARIA). Paper presented at: Alzheimer's Assoc. Int Conf. (AAIC), July 13-18, 2013; Boston, Abst 4-285. Available at: http://www.alzheimersanddementia.com/article/S1552-5260%2813%2902335-2/abstract. doi: 10.1016/j.jalz.2013.05.1678
  10. Rosen L, Pomfret M, Billinton A et al. Tolerability and preliminary pharmacodynamics after single doses of MEDI1814, a beta-amyloid 42 (AB42)-specific antibody, in mild-moderate Alzheimer’s disease. Paper presented at: 8th Clin. Trials Alzheimer's Dis. (CTAD) Conf.; November 5-7, 2015; Barcelona: Abst. OC25; Available at: http://www.ctad-alzheimer.com/sites/ctad.prod/files/files/THURSDAY%20NOVEMBER%205th%20%283%29.pdf
  11. Available at: https://integrity.thomson-pharma.com/integrity/xmlxsl/
  12. Davtyan H, Ghochikyan A, Petrushina I, Hovakimyan A, Davtyan A, Poghosyan A, Marleau AM, Movsesyan N, Kiyatkin A, Rasool S, Larsen AK, Madsen PJ, Wegener KM, Ditlevsen DK, Cribbs DH, Pedersen LO, Agadjanyan MG. Immunogenicity, efficacy, safety, and mechanism of action of epitope vaccine (Lu AF20513) for Alzheimer's disease: prelude to a clinical trial. J Neurosci. 2013;33(11):4923-4934. doi: 10.1523/JNEUROSCI.4672-12.2013
  13. Valera E, Spencer B, Masliah E. Immunotherapeutic Approaches Targeting Amyloid-β, α-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders. Neurotherapeutics. 2015. doi: 10.1007/s13311-015-0397-z.
  14. Novak M. Tau vaccine: Active immunization with misfolded tau protein attenuates tau pathology in the transgenic rat model of tauopathy. Alzheimer Dement. 2009;5(suppl 4):2-01-02.  doi: 10.1016/j.jalz.2009.05.246
  15. Sheridan C. Pivotal trials for beta-secretase inhibitors in Alzheimer's. Nat Biotechnol. 2015;33(2):115-116.  doi: 10.1038/nbt0215-115
  16. Hu Q, Cam J, Lake T, Cummings J, Esposito L, Yadon M-C, Snow A. Identification of Exebryl-1 and other novel small molecules as Tau protein aggregation. Paper presented at: Alzheimer's Assoc. Int Conf (AAIC); July 16-21, 2011. Paris: 2-529. Available at: http://www.alzheimersanddementia.com/article/S1552-5260(11)01541-X/abstract doi: 10.1016/j.jalz.2011.05.1398
  17. Froestl W, Pfeifer A, Muhs A. Cognitive enhancers (nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. disease-modifying drugs. J Alzheimers Dis. 2013;34(1):1-114.  doi: 10.3233/JAD-121729
  18. Dunkel P, Chai CLL, Sperlághd B, Huleatt PB, Matyus P. Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis. Expert Opin Investig Drugs. 2012;21(9):1267-1308. doi: 10.1517/13543784.2012.703178
  19. Available at: https://ClinicalTrials.gov/
  20. BELLUS Health Announces Partnership for the Development of BLU8499. BELLUS Health Press Release 2013, September 04. Available at: http://www.bellushealth.com/English/investors-and-news/press-releases/press-release-details/2012/BELLUS-Health-Announces-Partnership-for-the-Development-of-BLU84991130839/default.aspx
  21. Pepys MB, Herbert J, Hutchinson WL, Tennent GA, Lachmann HJ, Gallimore JR, Lovat LB, Bartfai T, Alanine A, Hertel C, Hoffmann T, Jakob-Roetne R, Norcross RD, Kemp JA, Yamamura K, Suzuki M, Taylor GW, Murray S, Thompson D, Purvis A, Kolstoe S, Wood SP, Hawkins PN. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature. 2002;417(6886):254-259.  doi: 10.1038/417254a
  22. Muggia F, Kudlowitz D. Novel taxanes. Anti-Cancer Drugs. 2014;25(5):593-598.  doi: 10.1097/CAD.0000000000000053
  23. Vasiliou S, Cole P, Gomez-Zaera M. Pharmacokinetics, pharmacodynamics, and safety of the novel BACE inhibitor BI1181181 after oral administration of single-ascending-doses in healthy subjects. Drugs Fut. 2011;36(10):783-792.  doi: 10.1358/dof.2011.036.10.1704837
  24. Navarro D, Castaner R, Fernandez-Forner D. NME digest. Drugs Fut. 2015;40(10):667-676. Available at: https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_toc_pr?p_JournalID=2&p_IssueID=1248
  25. Anand R, Seiberling M, Kamtchoua T, Pokorny R. Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers. Clin Pharmacokin. 2007;46(4):351-358.  doi: 10.2165/00003088-200746040-00007
  26. FGL-L. Drug Data Rep. 2006;28(11):1006. Available at: https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_toc_pr?p_JournalID=1&p_IssueID=852
  27. Eriksdotter-Jönhagen M, Linderoth B, Lind G, Aladellie L, Almkvist O, Andreasen N, Blennow K, Bogdanovic N, Jelic V, Kadir A, Nordberg A, Sundström E, Wahlund LO, Wall A, Wiberg M, Winblad B, Seiger A, Almqvist P, Wahlberg L. Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease. Dement. Geriatr Cogn Disord. 2012;33(1):18-28.  doi: 10.1159/000336051
  28. Jelinek GA, Weiland TJ, Hadgkiss EJ, Marck CH, Pereira N, van der Meer DM. Medication use in a large international sample of people with multiple sclerosis: Associations with quality of life, relapse rate and disability. Neurol Res. 2015;37(8):662-673.  doi: 10.1179/1743132815Y.0000000036
  29. Macdonald IR, Rockwood K, Martin E, Darvesh S. Cholinesterase inhibition in Alzheimer's disease: Is specificity the answer? J Alzheimer's Dis. 2014;42(2):379-384.  doi: 10.3233/JAD-140219
  30. Bhattacharya S, Maelicke A, Montag D. Nasal application of the galantamine pro-drug memogain slows down plaque deposition and ameliorates behavior in 5X familial alzheimer's disease mice. J Alzheimer's Dis. 2015;46(1):123-136.  doi: 10.3233/JAD-142421
  31. Tkachenko S, Ivachtchenko A, Khvat A, Okun I et al. Discovery and preclinical studies of AVN-322 highly selective and potent 5-HT6 antagonist for cognition enhancement in treating neurodegerative diseases. Paper presented at: 9th Int Conf Alzheimer Parkinson Dis (AD/PD); March 11-15, 2009. Available at: http://www.karger.com/ProdukteDB/miscArchiv/NDD_2009_006_s_1/pdf/945.pdf
  32. Yao J, Zhao LQ, Mao ZS, Chen SH, Wong KC, To J, Brinton RD. Potentiation of brain mitochondrial function by S-equol and R/S-equol estrogen receptor beta-selective phytoSERM treatments. Brain Res. 2013;1514:128-141.  doi: 10.1016/j.brainres.2013.02.021
  33. Kume K, Hanyu H, Sakurai H, Takada Y, Onumam T, Iwamoto T. Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer's disease. Geriatr Gerontol Int. 2012;12(2):207-214.  doi: 10.1111/j.1447-0594.2011.00746.x
  34. New NIH-funded memory drug moves into Phase 1 clinical study. National Institutes of Health (NIH) Press Release 2015, December 30. Available at: http://www.nih.gov/news-events/news-releases/new-nih-funded-memory-drug-moves-into-phase-1-clinical-study
  35. Shin JH, Lee YA, Lee JK, Lee YB, Cho W, Im DS, Lee JH, Yun BS, Springer JE, Gwag BJ. Concurrent blockade of free radical and microsomal prostaglandin E synthase-1-mediated PGE(2) production improves safety and efficacy in a mouse model of amyotrophic lateral sclerosis. J Neurochem. 2012;122(5):952-961.  doi: 10.1111/j.1471-4159.2012.07771.x
  36. Davtyan H, Ghochikyan A, Petrushina I, Hovakimyan A, Davtyan A, Poghosyan A, Marleau AM, Movsesyan N, Kiyatkin A, Rasool S, Larsen AK, Madsen PJ, Wegener KM, Ditlevsen DK, Cribbs DH, Pedersen LO, Agadjanyan MG. Immunogenicity, efficacy, safety, and mechanism of action of epitope vaccine (Lu AF20513) for Alzheimer's disease: prelude to a clinical trial. J Neurosci. 2013;33(11):4923-4934. doi: 10.1523/JNEUROSCI.4672-12.2013
  37. Butchart J, Brook L, Hopkins V, Teeling J, Püntener U, Culliford D, Sharples R, Sharif S, McFarlane B, Raybould R, Thomas R, Passmore P, Perry VH, Holmes C. Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial. Neurology. 2015;84(21):2161-2168. doi: 10.1212/WNL.0000000000001617
  38. Lee DS, Choi J, Kim SH, Kim S. Ameliorating effects of HX106N, a water-soluble botanical formulation, on abeta25-35-induced memory impairment and oxidative stress in mice. Biol Pharm Bull. 2014;37(6):954-960.  doi: 10.1248/bpb.b13-00906
  39. Schneeberger A, Mandler M, Otawa O, Zauner W, Mattner F, Schmidt W. Development of AFFITOPE vaccines for Alzheimer's disease (AD) - from concept to clinical testing. J Nutr Health Aging. 2009;13(3):264-267.  doi: 1007/s12603-009-0070-5
  40. Hickman DT, López-Deber MP, Ndao DM, Silva AB, Nand D, Pihlgren M, Giriens V, Madani R, St-Pierre A, Karastaneva H, Nagel-Steger L, Willbold D, Riesner D, Nicolau C, Baldus M, Pfeifer A, Muhs A. Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases. J Biol Chem. 2011;286(16):13966-13976. doi: 10.1074/jbc.M110.186338
  41. Tucker S, Möller C, Tegerstedt K, Lord A, Laudon H, Sjödahl J, Söderberg L, Spens E, Sahlin C, Waara ER, Satlin A, Gellerfors P, Osswald G, Lannfelt L. The murine version of BAN2401 (mAb158) selectively reduces amyloid-ßprotofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimer's Dis. 2015;43(2):575-588.  doi: 10.3233/JAD-140741
  42. Wang CY, Finstad CL, Walfield AM, Sia C, Sokoll KK, Chang TY, Fang XD, Hung CH, Hutter-Paier B, Windisch M. Site-specific UBITh((R)) amyloid-beta vaccine for immunotherapy of Alzheimer's disease. Vaccine. 2007;25(16):3041-3052. doi: 10.1016/j.vaccine.2007.01.031
  43. Laske C. Phase 3 trials of solanezumab and bapineuzumab for Alzheimer's disease. New Engl J Med. 2014;370(15):1459-1460. doi: 10.1056/NEJMc1402193#SA2
  44. Adolfsson O, Pihlgren M, Toni N, Varisco Y, Buccarello AL, Antoniello K, Lohmann S, Piorkowska K, Gafner V, Atwal JK, Maloney J, Chen M, Gogineni A, Weimer RM, Mortensen DL, Friesenhahn M, Ho C, Paul R, Pfeifer A, Muhs A, Watts RJ. An effector-reduced anti-beta-amyloid (Abeta) antibody with unique abetabinding properties promotes neuroprotection and glial engulfment of Abeta. J Neurosci. 2012;32(28):9677-9689. doi: 10.1523/JNEUROSCI.4742-11.2012
  45. Landen JW, Zhao Q, Cohen S, Borrie M, Woodward M, Billing CB. Jr, Bales K, Alvey C, McCush F, Yang J, Kupiec JW, Bednar MM. Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: A phase I, randomized, placebo-controlled, double-blind, dose-escalation study. Clin Neuropharmacol. 2013;36(1):14-23.  doi: 10.1097/WNF.0b013e31827db49b
  46. Maccecchini ML, Chang MY, Pan C, John V, Zetterberg H, Greig NH. Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-beta peptide and t levels: Target engagement, tolerability and pharmacokinetics in humans. J Neurol Neurosurg Psychiatry. 2012;83(9):894-902.  doi: 10.1136/jnnp-2012-302589
  47. Sinha S, Du ZM, Maiti P, Klaerner F-G, Schrader T, Wang C, Bitan G. Comparison of three amyloid assembly inhibitors: The sugar scyllo-inositol, the polyphenol epigallocatechin gallate, and the molecular tweezer CLR01. ACS Chem Neurosci. 2012;3(6):451-458.  doi: 10.1021/cn200133x
  48. Matijevic M, Watanabe H, Sato Y et al. A single dose of the beta-secretase inhibitor, E2609, decreases CSF BACE1 enzymatic activity in cynomolgus monkeys. Paper presented at: Alzheimer's Assoc. Int Conf (AAIC), July 18-23, 2015. Washington: 4-163. Available at: https://www.infona.pl/resource/bwmeta1.element.elsevier-7faa3953-81ea-398d-80d8-de084ed27a74. doi: 10.1016/j.jalz.2015.06.1870
  49. Takamura Y, Ono K, Matsumoto J, Yamada M, Nishijo H. Effects of the neurotrophic agent T-817MA on oligomeric amyloid-beta-induced deficits in long-term potentiation in the hippocampal CA1 subfield. Neurobiol Aging. 2014;35(3):532-536.  doi: 10.1016/j.neurobiolaging.2013.08.037
  50. Boxer AL, Lang AE, Grossman M et al. Davunetide in patients with progressive supranuclear palsy: A randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014;13(7):676-685.  doi: 10.1016/S1474-4422(14)70088-2
  51. Neurostem-AD' the treatment for Alzheimer's disease requested for phase 1.2a clinical trials. Medipost Press Release 2013, June 28. Available at: http://webcache.googleusercontent.com/search?q=cache:ATBCVQXFl3gJ:http://www.medi-post.com/2013/06/8254/%2BNeurostem-AD%27+the+treatment+for+Alzheimer%27s+disease+requested+for+phase+1.2a+clinical+trials&hl=ru&biw&bih&gbv=2&&ct=clnk
  52. Tuszynski MH, Yang JH, Barba D, U HS, Bakay RA, Pay MM, Masliah E, Conner JM, Kobalka P, Roy S, Nagahara AH. Nerve growth factor gene therapy activation of neuronal responses in Alzheimer disease. JAMA Neurol. 2015;72(10):1139-1147. doi: 10.1001/jamaneurol.2015.1807
  53. Gault LM, Meier A, Florian H, Ritchie CW, Tang Q, Othman A, Vie A. Efficacy and safety of the alpha7 agonist ABT-126 as a monotherapy treatment in mild-to-moderate Alzheimer's dementia: Results of a phase 2b trial. Paper presented at: Alzheimer's Assoc. Int Conf (AAIC); July 12-17, 2014; Copenhagen: Abst. 01-05-02. Available at: http://www.alzheimersanddementia.com/article/S1552-5260(14)00209-X/abstract doi: 10.1016/j.jalz.2014.04.081
  54. Froelich L, Ashwood T, Nilsson J, Eckerwall G. Effects of AZD3480 on cognition in patients with mild-to-moderate Alzheimer's disease: A phase IIb dose-finding study. J Alzheimer's Dis. 2011;24(2):363-374.  doi: 10.3233/JAD-2011-101554
  55. Ramirez MJ, Lai MK, Tordera RM, Francis PT. Serotonergic therapies for cognitive symptoms in Alzheimer's disease: Rationale and current status. Drugs. 2014;74(7):729-736.  doi: 10.1007/s40265-014-0217-5
  56. Maher-Edwards G, Dixon R, Hunter J, Gold M, Hopton G, Jacobs G, Hunter J, Williams P. SB-742457 and donepezil in Alzheimer disease: A randomized, placebo-controlled study. Int J Geriatr Psychiatry. 2011;26(5):536-544.  doi: 10.1002/gps.2562
  57. Rinne JO, Wesnes K, Hänninen J, Murphy M, Riordan H, Rouru J. Safety and efficacy of ORM-12741 on cognitive and behavioral symptoms in patients with Alzheimer's disease: A randomized, double-blind, proof-of-concept study. J Neurol Sci. 2013;333(suppl 1):322.  doi: 10.1016/j.jns.2013.07.1199
  58. Chumakov I, Nabirotchkin S, Cholet N, Milet A, Boucard A, Toulorge D, Pereira Y, Graudens E, Traoré S, Foucquier J, Guedj M, Vial E, Callizot N, Steinschneider R, Maurice T, Bertrand V, Scart-Grès C, Hajj R, Cohen D. Combining two repurposed drugs as a promising approach for Alzheimer's disease therapy. Sci Rep. 2015;5:7608. doi: 10.1038/srep07608
  59. Lahmy V, Meunier J, Malmstroem S, Naert G, Givalois L, Kim SH, Villard V, Vamvakides A, Maurice T. Blockade of Tau hyperphosphorylation and Abeta1-42 generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and sigma1 receptor agonist, in a nontransgenic mouse model of Alzheimer's disease. Neuropsychopharmacology. 2013;38(9):1706-1723. doi: 10.1038/npp.2013.70
  60. Cudkowicz M, Bozik ME, Ingersoll EW, Miller R, Mitsumoto H, Shefner J, Moore DH, Schoenfeld D, Mather JL, Archibald D, Sullivan M, Amburgey C, Moritz J, Gribkoff VK. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. Nat Med. 2011;17(12):1652-1656. doi: 10.1038/nm.2579
  61. Chiu W-H, Depboylu C, Hermanns G, Maurer L, Windolph A, Oertel WH, Ries V, Hoeglinger GU. Long-term treatment with L-DOPA or pramipexole affects adult neurogenesis and corresponding non-motor behavior in a mouse model of Parkinson's disease. Neuropharmacology. 2015;95:367-376.  doi: 10.1016/j.neuropharm.2015.03.020
  62. Weinreb O, Amit T, Bar-Am O, Youdim MB. Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory activities for Alzheimer's disease treatment. Curr Drug Targets. 2012;13(4):483-494.  doi: 10.2174/138945012799499794
  63. Weinreb O, Badinter F, Amit T, Bar-Am O, Youdim MB. Effect of long-term treatment with rasagiline on cognitive deficits and related molecular cascades in aged mice. Neurobiol Aging. 2015;36(9):2628-2636. doi: 10.1016/j.neurobiolaging.2015.05.009
  64. Andreasen N, Akenine U, Al-Tawil N et al. Brain MAO-B inhibition in healthy elderly and people with Alzheimer's disease after oral administration of RO4602522. Paper presented at: Alzheimer's Assoc Int Conf (AAIC); July 13-18, 2015; Boston: Abst P3-300. Available at: http://www.alzheimersanddementia.com/article/S1552-5260(13)02031-1/abstract doi: 10.1016/j.jalz.2013.05.1374
  65. Shaddinger BC, Xu YM, Roger JH, Macphee CH, Handel M, Baidoo CA, Magee M, Lepore JJ, Sprecher DL. Platelet aggregation unchanged by lipoprotein-associated phospholipase A2 inhibition: Results from an in vitro study and two randomized phase I trials. PLoS ONE 2014.Т.9.№.1.С.e83094. Available at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083094  doi: 10.1371/journal.pone.0083094
  66. Rosenbrock H, Marti A, Koros E, Runge F, Fuchs H, Giovannini R, Dorner-Ciossek C. Improving synaptic plasticity and cognitive function in rodents by the novel phosphodiesterase 9A inhibitor BI 409306. Paper presented at: Alzheimer's Assoc .Int. Conf. (AAIC); July 18-23, 2015; Washington: 4246. Available at: https://www.researchgate.net/publication/287126826_Improving_synaptic_plasticity_and_cognitive_function_in_rodents_by_the_nov doi: 10.1016/j.jalz.2015.06.852
  67. Sun MK, Hongpaisan J, Lim CS, Alkon DL. Bryostatin-1 restores hippocampal synapses and spatial learning and memory in adult fragile x mice. J Pharmacol Exp Ther. 2014;349(3):393-401.  doi: 10.1124/jpet.114.214098
  68. Pradal J, Zuluaga M-F, Maudens P, Waldburger J-M, Seemayer CA, Doelker E, Gabay C, Jordan O, Allemann E. Intra-articular bioactivity of a p38 MAPK inhibitor and development of an extended-release system. Eur J Pharm Biopharm. 2015;93:110-117.  doi: 10.1016/j.ejpb.2015.03.017
  69. Sanchez PE, Zhu L, Verret L, Vossel KA, Orr AG, Cirrito JR, Devidze N, Ho K, Yu GQ, Palop JJ, Mucke L. Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. Proc Natl Acad Sci USA. 2012;109(42):2895-2903. doi: 10.1073/pnas.1121081109
  70. Sugiyama A, Saitoh A, Inagaki M, Oka J-I, Yamada M. Systemic administration of riluzole enhances recognition memory and facilitates extinction of fear memory in rats. Neuropharmacology. 2015;97:322-328.  doi: 10.1016/j.neuropharm.2015.06.007
  71. Garcia JA, Elson P, Tyler A, Triozzi P, Dreicer R. Sargramostim (GM-CSF) and lenalidomide in castration-resistant prostate cancer (CRPC): Results from a phase I-II clinical trial. Urol Oncol. 2014;32(1):33.11-17.  doi: 10.1016/j.urolonc.2012.12.004
  72. Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, Brewer JB, Rissman RA, Paul RR. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015;85(16):1383-1391. doi: 10.1212/WNL.0000000000002035
  73. Zhai P, Xia CL, Tan JH, Li D, Ou TM, Huang SL, Gu LQ, Huang ZS. Syntheses And Evaluation Of Asymmetric Curcumin Analogues As Potential Multifunctional Agents For The Treatment Of Alzheimer's Disease. Curr Alzheimer Res. 2015;12(5):403-414.  doi: 10.2174/1567205012666150504151120
  74. Butchart J, Brook L, Hopkins V, Teeling J, Püntener U, Culliford D, Sharples R, Sharif S, McFarlane B, Raybould R, Thomas R, Passmore P, Perry VH, Holmes C. Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial. Neurology. 2015;84(21):2161-2168. doi: 10.1212/WNL.0000000000001617
  75. Sun XJ, Zhao L, Zhao N, Pan XL, Fei GQ, Jin LR, Zhong CJ. Benfotiamine prevents increased β-amyloid production in HEK cells induced by high glucose. Neurosci Bull. 2012;28(5):561-566.  doi: 10.1007/s12264-012-1264-0
  76. Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, Wilson DA, Landreth GE. ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science. 2012;335(6075):1503-1506. doi: 10.1126/science.1217697
  77. Fukasawa H, Nakagomi M, Yamagata N, Katsuki H, Kawahara K, Kitaoka K, Miki T, Shudo K. Tamibarotene: a candidate retinoid drug for Alzheimer's disease. Biol Pharm Bull. 2012;35(8):1206-1212. doi: 10.1248/bpb.b12-00314
  78. Ormerod AD, Thind CK, Rice SA, Reid IC, Williams JH, McCaffery PJ. Influence of isotretinoin on hippocampal-based learning in human subjects. Psychopharmacology (Berl). 2012;221(4):667-674.  doi: 10.1007/s00213-011-2611-y
  79. Lerner AJ, Gustaw-Rothenberg K, Smyth S, Casadesus G. Retinoids for treatment of Alzheimer's disease. Biofactors. 2012;38(2):84-89.  doi: 10.1002/biof.196
  80. Kelley BJ, Glasser S. Cognitive effects of statin medications. CNS Drugs. 2014;28(5):411-419.  doi: 10.1007/s40263-014-0147-5
  81. Kurata T, Miyazaki K, Kozuki M, Morimoto N, Ohta Y, Ikeda Y, Abe K. Progressive neurovascular disturbances in the cerebral cortex of Alzheimer's disease-model mice: protection by atorvastatin and pitavastatin. Neuroscience. 2011;197:358-368.  doi: 10.1016/j.neuroscience.2011.09.030
  82. Barone E, Mancuso C, Di Domenico F, Sultana R, Murphy MP, Head E, Butterfield DA. Biliverdin reductase-A: a novel drug target for atorvastatin in a dog pre-clinical model of Alzheimer disease. J Neurochem. 2012;120(1):135-146.  doi: 10.1111/j.1471-4159.2011.07538.x
  83. Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, Aisen PS. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology. 2011;77(6):556-563.  doi: 10.1212/WNL.0b013e318228bf11
  84. Liang T, Li R, Cheng O. Statins for Treating Alzheimer's Disease: Truly Ineffective? Eur Neurol. 2015;73(5-6):360-366.  doi: 10.1159/000382128
  85. Godyń J, Jończyk J, Panek D, Malawska B. Therapeutic strategies for Alzheimer's disease in clinical trials. Pharmacological Reports. 2016;68(1):127-138.  doi: 10.1016/j.pharep.2015.07.006
  86. Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C, Craft S. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's diseasedementia. J Alzheimers Dis. 2015;44(3):897-906.  doi: 10.3233/JAD-141791
  87. Egefjord L, Gejl M, Møller A, Brændgaard H, Gottrup H, Antropova O, Møller N, Poulsen HE, Gjedde A, Brock B, Rungby J. Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimer´s disease - protocol for a controlled, randomized double-blinded trial. Dan Med J. 2012;59(10):4519. Available at: http://www.danmedj.dk/portal/page/portal/danmedj.dk/dmj_forside/PAST_ISSUE/2012/DMJ_2012_10/A4519
  88. Bomba M, Ciavardelli D, Silvestri E, Canzoniero LM, Lattanzio R, Chiappini P, Piantelli M, Di Ilio C, Consoli A, Sensi SL. Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals. Cell Death Dis. 2013;4:612.  doi: 10.1038/cddis.2013.139
  89. Shah RC, Matthews DC, Andrews RD, Capuano AW, Fleischman DA, VanderLugt JT, Colca JR. An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in patients with mild Alzheimer's disease. Curr Alzheimer Res. 2014;11(6):564-573.  doi: 10.2174/1567205011666140616113406
  90. Neumann U, Rueeger H, Machauer R, Veenstra SJ, Lueoend RM, Tintelnot-Blomley M, Laue G, Beltz K, Vogg B, Schmid P, Frieauff W, Shimshek DR, Staufenbiel M, Jacobson LH. A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice. Mol Neurodegener. 2015;10:44.  doi: 10.1186/s13024-015-0033-8
  91. Garakani A, Murrough JW, Iosifescu DV. Advances in Psychopharmacology for Anxiety Disorders. FOCUS. 2014;12(2):152-162.  doi: 10.1176/appi.focus.12.2.152
  92. Lavrovsky Y, Ivanchtchenko AV, Morozova M, Salimov RM, Kasey V. Preclinical and early clinical studies of AVN-101, a novel balanced molecule for the treatment of Alzheimer's disease. Paper presented at: 13th Int. Conf. Alzheimer's Dis. Relat.Disord. (ICAD); July 10-15, 2010; Honolulu: 3-442. Available at: http://www.alzheimersanddementia.com/article/S1552-5260(10)02104-7/abstract doi: 10.1016/j.jalz.2010.05.1984
  93. Hu C, Adedokun O, Ito K, Raje S, Lu M. Confirmatory population pharmacokinetic analysis for bapineuzumab phase 3 studies in patients with mild to moderate Alzheimer's disease. J Clin Pharmacol. 2015;55(2):221-229.  doi: 10.1002/jcph.393
  94. Jarvis L. Alzheimer’s Next Chapter. Paper presented at: Cen ACS Org, June 1, 2015;11-15. Available at: http://cen.acs.org/articles/93/i22/Next-Chapter-Treating-Alzheimers.html
  95. Sevigny J, Chiao P, Williams T, Chen T, Ling Y, O'Gorman J, Hock C, Ntsch RM, Sandrock A. Aducanumab (BIIB037), an anti-amyloid beta monoclonal antibody, in patients with prodromal or mild Alzheimer's disease: Interim results of a randomized, double-blind, placebo-controlled, phase 1B study. Paper presented at: Alzheimer's Assoc. Int Conf (AAIC); July 18-23, 2015; Washington: 4484. Available at: http://www.alzheimersanddementia.com/article/S1552-5260(15)02517-0/abstract doi: 10.1016/j.jalz.2015.07.367
  96. Jacobsen H, Ozmen L, Caruso A, Narquizian R, Hilpert H, Jacobsen B, Terwel D, Tanghe A, Bohrmann B. Combined treatment with a BACE inhibitor and anti-Abeta antibody gantenerumab enhances amyloid reduction in APPLondon mice. J Neurosci. 2014;34(35):11621-11630. doi: 10.1523/JNEUROSCI.1405-14.2014
  97. Relkin N. Clinical trials of intravenous immunoglobulin for Alzheimer's disease. J Clin Immunol. 2014;34(suppl 1):74-79.  doi: 10.1007/s10875-014-0041-4
  98. Yan R, Vassar R. Targeting the β secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol. 2014;13(3):319-329.  doi: 10.1016/S1474-4422(13)70276-X
  99. Wischik CM, Staff RT, Wischik DJ, Bentham P, Murray AD, Storey JM, Kook KA, Harrington CR. Tau aggregation inhibitor therapy: An exploratory phase 2 study in mild or moderate Alzheimer's disease. J Alzheimer's Dis. 2015;44(2):705-720.  doi: 10.3233/JAD-142874
  100. Baddeley TC, McCaffrey J, Storey JM, Cheung JK, Melis V, Horsley D, Harrington CR, Wischik C.M. Complex disposition of methylthioninium redox forms determines efficacy in tau aggregation inhibitor therapy for Alzheimer's diseas. J Pharmacol Exp Ther. 2015;352(1):110-118.  doi: 10.1124/jpet.114.219352
  101. Wilkinson D, Windfeld K, Colding-Jorgensen E. Safety and efficacy of idalopirdine, a 5-HT6 receptor antagonist, in patients with moderate Alzheimer's disease (LADDER): A randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2014;13(11):1092-1099. doi: 10.1016/S1474-4422(14)70198-X
  102. Barbier AJ, Hilhorst M, Van Vliet A, Snyder P, Palfreyman MG, Gawryl M, Dgetluck N, Massaro M, Tiessen R, Timmerman W, Hilt DC. Pharmacodynamics, pharmacokinetics, safety, and tolerability of encenicline, a selective α7 nicotinic receptor partial agonist, in single ascending-dose and bioavailability studies. Clin Ther. 2015;37(2):311-324.  doi: 10.1016/j.clinthera.2014.09.013
  103. Mandavilli A. The amyloid code. Nat Med. 2006;12(7):747-751.  doi: 10.1038/nm0706-747
  104. Beaulieu-Abdelahad D, Kennelly S, Paris D, Lawlor B, Abdullah L, Ait-Ghezala G, Crawford F, Kenny RA, Bachmeier C. Mechanism of action of new Alzheimer's therapeutic in phase III clinical trials. Paper presented at: Alzheimer's Assoc. Int Conf (AAIC); July 16-21, 2011; Paris: 4-428. Available at: http://www.alzheimersanddementia.com/article/S1552-5260(11)02843-3/abstract doi: 10.1016/j.jalz.2011.09.124
  105. Sato T, Hanyu H, Hirao K, Kanetaka H, Sakurai H, Iwamoto T. Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease. Neurobiol Aging. 2011;32(9):1626-1633. doi: 10.1016/j.neurobiolaging.2009.10.009
  106. Shen C, Chen L, Jiang L, Lai TYY. Neuroprotective effect of epigallocatechin-3-gallate in a mouse model of chronic glaucoma. Neurosci Lett. 2015;600:132-136.  doi: 10.1016/j.neulet.2015.06.002
  107. Gutzmann H, Hadler D. Sustained efficacy and safety of idebenone in the treatment of Alzheimer's disease: update on a 2-year double-blind multicentre study. J Neural Transm Suppl. 1998;54:301-310.  doi: 10.1007/978-3-7091-7508-8_30
  108. Bukatina EE, Grigor'eva IV, Sokol'chik EI. The effectiveness of amiridin in senile dementia of the Alzheimer's type. Neurosci Behav Physiol. 1993;23(1):83-89.  doi: 10.1007/BF01182643
  109. Qian ZM, Ke Y, Huperzine A. Is it an Effective Disease-Modifying Drug for Alzheimer's Disease? Front Aging Neurosci. 2014;6:216.  doi: 10.3389/fnagi.2014.00216
  110. Yang G, Wang Y, Sun J, Zhang K, Liu J. Ginkgo Biloba for Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Curr Top Med Chem. 2016;16(5):520-528.  doi: 10.2174/1568026615666150813143520
  111. Farias GA, Guzman-Martinez L, Delgado C, Maccioni RB. Nutraceuticals: A novel concept in prevention and treatment of Alzheimer's disease and related disorders. J Alzheimer's Dis. 2014;42(2):357-367.  doi: 10.3233/JAD-132741
  112. Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F. New pharmacological strategies for treatment of Alzheimer's disease: focus on disease modifying drugs. Br J Clin Pharmacol. 2012;73(4):504-517.  doi: 10.1111/j.1365-2125.2011.04134.x
  113. Carreiras MC, Mendes E, Perry MJ, Francisco AP, Marco-Contelles J. The multifactorial nature of Alzheimer's disease for developing potential therapeutics. Curr Top Med Chem. 2013;13(15):1745-1770. doi: 10.2174/15680266113139990135
  114. Youdim MB. Multi target neuroprotective and neurorestorative anti-Parkinson and anti-Alzheimer drugs ladostigil and m30 derived from rasagiline. Exp Neurobiol. 2013;22(1):1-10.  doi: 10.5607/en.2013.22.1.1
  115. Ustyugov A, Shevtsova E, Bachurin S. Novel Sites of Neuroprotective Action of Dimebon (Latrepirdine). Mol Neurobiol. 2015;52(2):970-978.  doi: 10.1007/s12035-015-9249-4
  116. Corbett A, Pickett J, Burns A, Corcoran J, Dunnett SB, Edison P, Hagan JJ, Holmes C, Jones E, Katona C, Kearns I, Kehoe P, Mudher A, Passmore A, Shepherd N, Walsh F, Ballard C. Drug repositioning for Alzheimer's disease. Nat Rev Drug Discov. 2012;11(11):833-846.  doi: 10.1038/nrd3869

Close metadata

Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Contact us
If you have any questions, complaints or suggestions, please use this feedback form.
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.
Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.