Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Review Article

Recent Updates on the Development of Therapeutics for the Targeted Treatment of Alzheimer’s Disease

Author(s): Shivam Rajput, Rishabha Malviya*, Shiv Bahadur and Dinesh Puri

Volume 29, Issue 35, 2023

Published on: 24 November, 2023

Page: [2802 - 2813] Pages: 12

DOI: 10.2174/0113816128274618231105173031

Price: $65

conference banner
Abstract

Alzheimer's disease (AD) is a complicated, multifaceted, irreversible, and incurable neurotoxic old age illness. Although NMDA (N-methyl D-aspartate)-receptor antagonists, cholinesterase repressors, and their pairings have been approved for the treatment, they are useful for short symptomatic relief. Researchers throughout the globe have been constantly working to uncover the therapy of Alzheimer's disease as new candidates must be determined, and newer treatment medicines must be developed. The aim of this review is to address recent advances in medication research along with new Alzheimer's disease therapy for diverse targets. Information was gathered utilizing a variety of internet resources as well as websites, such as ALZFORUM (alzforum.org) and clinicaltrials.gov. In contrast to other domains, the proposed medicines target amyloids (secretases, A42 generation, neuroinflammation, amyloid precipitation, and immunization), tau proteins (tau phosphorylation/aggregation and immunotherapy), and amyloid deposition. Despite tremendous advancement in our understanding of the underlying pathophysiology of Alzheimer's disease, the FDA (Food and Drug Administration) only approved aducanumab for diagnosis and treatment in 2003. Hence, novel treatment tactics are needed to find and develop therapeutic medicines to combat Alzheimer's disease.

Keywords: Neurodegeneration, Alzheimer’s disease, potential targets, therapeutics, neural disorders, pathophysiology.

« Previous Next »
[1]
Uwishema O, Mahmoud A, Sun J, et al. Is Alzheimer’s disease an infectious neurological disease? A review of the literature. Brain Behav 2022; 12(8): e2728.
[http://dx.doi.org/10.1002/brb3.2728] [PMID: 35879909]
[2]
Berchtold NC, Cotman CW. Evolution in the conceptualization of dementia and Alzheimer’s disease: Greco-Roman period to the 1960s. Neurobiol Aging 1998; 19(3): 173-89.
[http://dx.doi.org/10.1016/S0197-4580(98)00052-9] [PMID: 9661992]
[3]
Gupta S, Nair A, Jhawat V, et al. Unwinding complexities of diabetic Alzheimer by potent novel molecules. Am J Alzheimers Dis Other Demen 2020; 35
[http://dx.doi.org/10.1177/1533317520937542] [PMID: 32864980]
[4]
Tucker S, Möller C, Tegerstedt K, et al. The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis 2014; 43(2): 575-88.
[http://dx.doi.org/10.3233/JAD-140741] [PMID: 25096615]
[5]
Alberti S, Hyman AA. Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing. Nat Rev Mol Cell Biol 2021; 22(3): 196-213.
[http://dx.doi.org/10.1038/s41580-020-00326-6] [PMID: 33510441]
[6]
Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele ϵ 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 1993; 43(8): 1467-72.
[http://dx.doi.org/10.1212/WNL.43.8.1467] [PMID: 8350998]
[7]
Bellenguez C, Küçükali F, Jansen IE, et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet 2022; 54(4): 412-36.
[http://dx.doi.org/10.1038/s41588-022-01024-z] [PMID: 35379992]
[8]
Initiation of new phase iii clinical study (ahead 3-45) of ban2401 preclinical (asymptomatic) Alzheimer’s disease [Internet]. Available from: https://www.eisai.com/news/2020/news202042.html Eisai.com. [cited 2022 Apr 8].
[9]
Ihara M, Saito S. Drug repositioning for Alzheimer’s disease: Finding hidden clues in old drugs. J Alzheimers Dis 2020; 74(4): 1013-28.
[http://dx.doi.org/10.3233/JAD-200049] [PMID: 32144994]
[10]
Ansari MA, Scheff SW. Oxidative stress in the progression of Alzheimer disease in the frontal cortex. J Neuropathol Exp Neurol 2010; 69(2): 155-67.
[http://dx.doi.org/10.1097/NEN.0b013e3181cb5af4] [PMID: 20084018]
[11]
Saharan S, Mandal PK. The emerging role of glutathione in Alzheimer’s disease. J Alzheimers Dis 2014; 40(3): 519-29.
[http://dx.doi.org/10.3233/JAD-132483] [PMID: 24496077]
[12]
Desai RJ, Varma VR, Gerhard T, et al. Targeting abnormal metabolism in Alzheimer’s disease: The drug repurposing for effective Alzheimer’s medicines (DREAM) study. Alzheimers Dement (N Y) 2020; 6(1): e12095.
[http://dx.doi.org/10.1002/trc2.12095] [PMID: 33304987]
[13]
Kim TW. Drug repositioning approaches for the discovery of new therapeutics for Alzheimer’s disease. Neurotherapeutics 2015; 12(1): 132-42.
[http://dx.doi.org/10.1007/s13311-014-0325-7] [PMID: 25549849]
[14]
Corbett A, Pickett J, Burns A, et al. Drug repositioning for Alzheimer’s disease. Nat Rev Drug Discov 2012; 11(11): 833-46.
[http://dx.doi.org/10.1038/nrd3869] [PMID: 23123941]
[15]
Howard R, Zubko O, Bradley R, et al. Minocycline at 2 different dosages vs. placebo for patients with mild Alzheimer disease: A randomized clinical trial. JAMA Neurol 2020; 77(2): 164-74.
[http://dx.doi.org/10.1001/jamaneurol.2019.3762] [PMID: 31738372]
[16]
Maqbool M, Mobashir M, Hoda N. Pivotal role of glycogen synthase kinase-3: A therapeutic target for Alzheimer’s disease. Eur J Med Chem 2016; 107: 63-81.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.018] [PMID: 26562543]
[17]
Athar T, Al Balushi K, Khan SA. Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease. Mol Biol Rep 2021; 48(7): 5629-45.
[http://dx.doi.org/10.1007/s11033-021-06512-9] [PMID: 34181171]
[18]
Golde TE. The Abeta hypothesis: Leading us to rationally-designed therapeutic strategies for the treatment or prevention of Alzheimer disease. Brain Pathol 2005; 15(1): 84-7.
[http://dx.doi.org/10.1111/j.1750-3639.2005.tb00104.x] [PMID: 15779241]
[19]
Selkoe DJ. Clearing the brain’s amyloid cobwebs. Neuron 2001; 32(2): 177-80.
[http://dx.doi.org/10.1016/S0896-6273(01)00475-5] [PMID: 11683988]
[20]
Montoliu-Gaya L, Villegas S. Protein structures in Alzheimer’s disease: The basis for rationale therapeutic design. Arch Biochem Biophys 2015; 588: 1-14.
[http://dx.doi.org/10.1016/j.abb.2015.10.005] [PMID: 26475676]
[21]
de Heus RAA, de Jong DLK, Lawlor BL, Claassen JAHR. Longitudinal changes in the control mechanisms for blood pressure and cerebral blood flow in Alzheimer’s disease: Secondary results of a randomized controlled trial. Cerebral Circulation - Cognition and Behavior 2021; 2: 100024.
[http://dx.doi.org/10.1016/j.cccb.2021.100024] [PMID: 36324723]
[22]
Elliott C, Rojo AI, Ribe E, et al. A role for APP in Wnt signalling links synapse loss with β-amyloid production. Transl Psychiatry 2018; 8(1): 179.
[http://dx.doi.org/10.1038/s41398-018-0231-6] [PMID: 30232325]
[23]
Santana S, Recuero M, Bullido MJ, Valdivieso F, Aldudo J. Herpes simplex virus type I induces the accumulation of intracellular β-amyloid in autophagic compartments and the inhibition of the non-amyloidogenic pathway in human neuroblastoma cells. Neurobiol Aging 2012; 33(2): 430.e19-33.
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.12.010] [PMID: 21272962]
[24]
Lerchundi R, Neira R, Valdivia S, et al. Tau cleavage at D421 by caspase-3 is induced in neurons and astrocytes infected with herpes simplex virus type 1. J Alzheimers Dis 2011; 23(3): 513-20.
[http://dx.doi.org/10.3233/JAD-2010-101386] [PMID: 21098975]
[25]
Mahla RS. Stem cells applications in regenerative medicine and disease therapeutics. Int J Cell Biol 2016. Oct;2016
[http://dx.doi.org/10.1155/2016/6940283]
[26]
Lyon L. Stem cell therapies in neurology: The good, the bad and the unknown. Brain 2018; 141(10): e77.
[http://dx.doi.org/10.1093/brain/awy221] [PMID: 30202947]
[27]
Liu Y, Weick JP, Liu H, et al. Medial ganglionic eminence–like cells derived from human embryonic stem cells correct learning and memory deficits. Nat Biotechnol 2013; 31(5): 440-7.
[http://dx.doi.org/10.1038/nbt.2565] [PMID: 23604284]
[28]
Liu X, Li F, Stubblefield EA, et al. Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Res 2012; 22(2): 321-32.
[http://dx.doi.org/10.1038/cr.2011.181] [PMID: 22105488]
[29]
Wang SM, Lee CU, Lim HK. Stem cell therapies for Alzheimer’s disease. Curr Opin Psychiatry 2019; 32(2): 105-16.
[http://dx.doi.org/10.1097/YCO.0000000000000478] [PMID: 30557266]
[30]
Sharma RR, Pollock K, Hubel A, McKenna D. Mesenchymal stem or stromal cells: A review of clinical applications and manufacturing practices. Transfusion 2014; 54(5): 1418-37.
[http://dx.doi.org/10.1111/trf.12421] [PMID: 24898458]
[31]
Martini S, Castellini L, Parladori R, Paoletti V, Aceti A, Corvaglia L. Free radicals and neonatal brain injury: From underlying pathophysiology to antioxidant treatment perspectives. Antioxidants 2021; 10(12): 2012.
[http://dx.doi.org/10.3390/antiox10122012] [PMID: 34943115]
[32]
Farlow M, Anand R, Messina J Jr, Hartman R, Veach J. A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur Neurol 2000; 44(4): 236-41.
[http://dx.doi.org/10.1159/000008243] [PMID: 11096224]
[33]
Hey JA, Koelsch G, Bilcer G, et al. Single dose administration of the β-secretase inhibitor CTS21166 (ASP1720) reduces plasma Aβ40 in human subjects. International Conference on Alzheimer’s Disease (ICAD) Jul 26.
[34]
Husain A, Balushi K A, Akhtar MJ, Khan SA. Coumarin linked heterocyclic hybrids: A promising approach to develop multi target drugs for Alzheimer’s disease. J Mol Struct 2021; 1241: 130618.
[http://dx.doi.org/10.1016/j.molstruc.2021.130618]
[35]
Eketjäll S, Janson J, Kaspersson K, et al. AZD3293: A novel, orally active BACE1 inhibitor with high potency and permeability and markedly slow off-rate kinetics. J Alzheimers Dis 2016; 50(4): 1109-23.
[http://dx.doi.org/10.3233/JAD-150834] [PMID: 26890753]
[36]
Sharma K. Cholinesterase inhibitors as Alzheimer’s therapeutics (Review). Mol Med Rep 2019; 20(2): 1479-87.
[PMID: 31257471]
[37]
Lipton SA, Nicotera P. Calcium, free radicals and excitotoxins in neuronal apoptosis. Cell Calcium 1998; 23(2-3): 165-71.
[http://dx.doi.org/10.1016/S0143-4160(98)90115-4] [PMID: 9601612]
[38]
Mirakhori F, Moafi M, Milanifard M, Tahernia H. Diagnosis and treatment methods in Alzheimer’s patients based on modern techniques: The orginal article. J Pharm Negat Results 2022; 1889-907.
[39]
Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med 2012; 366(10): 893-903.
[http://dx.doi.org/10.1056/NEJMoa1106668] [PMID: 22397651]
[40]
Takeuchi R, Shinozaki K, Nakanishi T, Tamai I. local drug–drug interaction of donepezil with cilostazol at breast cancer resistance protein (ABCG2) increases drug accumulation in heart. Drug Metab Dispos 2015; 44(1): 68-74.
[http://dx.doi.org/10.1124/dmd.115.066654] [PMID: 26467765]
[41]
Galantamine -Information sheet for primary care prescribers [Internet]. Nhs.uk. Available from: https://www.nottsapc.nhs.uk/media/1068/dementia-galantamine-information-sheet.pdf [cited 2022 May 3].
[42]
Birks JS, Evans JG. Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev 2015; 4.
[http://dx.doi.org/10.1002/14651858.CD001191.pub3]
[43]
Kuns B, Rosani A, Varghese D. Memantine StatPearls 2022. 2023 Jan.
[44]
Benek O, Korabecny J, Soukup O. A perspective on multi-target drugs for Alzheimer’s disease. Trends Pharmacol Sci 2020; 41(7): 434-45.
[http://dx.doi.org/10.1016/j.tips.2020.04.008] [PMID: 32448557]
[45]
Ladostigil. Available from: https://www.alzforum.org/therapeutics/ladostigil [cited 2022 Jul 1].
[46]
Snyder GL, Vanover KE, Zhu H, et al. Functional profile of a novel modulator of serotonin, dopamine, and glutamate neurotransmission. Psychopharmacology (Berl) 2015; 232(3): 605-21.
[http://dx.doi.org/10.1007/s00213-014-3704-1] [PMID: 25120104]
[47]
Atri A, Frölich L, Ballard C, et al. Effect of idalopirdine as adjunct to cholinesterase inhibitors on change in cognition in patients with Alzheimer disease: Three randomized clinical trials. JAMA 2018; 319(2): 130-42.
[http://dx.doi.org/10.1001/jama.2017.20373] [PMID: 29318278]
[48]
Ruthenberg K. About the futile dream of an entirely riskless and fully effective remedy: Thalidomide. InEthics of chemistry: From poison gas to climate engineering . 2021; pp. 141-67.
[49]
Langedijk J, Mantel-Teeuwisse AK, Slijkerman DS, Schutjens MHDB. Drug repositioning and repurposing: Terminology and definitions in literature. Drug Discov Today 2015; 20(8): 1027-34.
[http://dx.doi.org/10.1016/j.drudis.2015.05.001] [PMID: 25975957]
[50]
Khan SA, Al-Balushi K. Combating COVID-19: The role of drug repurposing and medicinal plants. J Infect Public Health 2021; 14(4): 495-503.
[http://dx.doi.org/10.1016/j.jiph.2020.10.012] [PMID: 33743371]
[51]
Hubsher G, Haider M, Okun MS. Amantadine: The journey from fighting flu to treating Parkinson disease. Neurology 2012; 78(14): 1096-9.
[http://dx.doi.org/10.1212/WNL.0b013e31824e8f0d] [PMID: 22474298]
[52]
Kumar N, Gahlawat A, Kumar RN, Singh YP, Modi G, Garg P. Drug repurposing for Alzheimer’s disease: in silico and in vitro investigation of FDA-approved drugs as acetylcholinesterase inhibitors. J Biomol Struct Dyn 2022; 40(7): 2878-92.
[http://dx.doi.org/10.1080/07391102.2020.1844054] [PMID: 33170091]
[53]
Daly T, Epelbaum S. The accelerated approval of aducanumab invites a rethink of the current model of drug development for Alzheimer’s disease. AJOB Neurosci 2022; 1-4.
[http://dx.doi.org/10.1080/21507740.2022.2129858] [PMID: 35263240]
[54]
Bauzon J, Lee G, Cummings J. Repurposed agents in the Alzheimer’s disease drug development pipeline. Alzheimers Res Ther 2020; 12(1): 98.
[http://dx.doi.org/10.1186/s13195-020-00662-x] [PMID: 32807237]
[55]
Alhazmi HA, Albratty M. An update on the novel and approved drugs for Alzheimer disease. Saudi Pharm J 2022; 30(12): 1755-64.
[http://dx.doi.org/10.1016/j.jsps.2022.10.004] [PMID: 36601504]
[56]
Kehoe PG, Blair PS, Howden B, et al. The rationale and design of the reducing pathology in Alzheimer’s disease through angiotensin targeting (RADAR) trial. J Alzheimers Dis 2017; 61(2): 803-14.
[http://dx.doi.org/10.3233/JAD-170101] [PMID: 29226862]
[57]
Ballard C, Aarsland D, Cummings J, et al. Drug repositioning and repurposing for Alzheimer disease. Nat Rev Neurol 2020; 16(12): 661-73.
[http://dx.doi.org/10.1038/s41582-020-0397-4] [PMID: 32939050]
[58]
Liu XY, Yang LP, Zhao L. Stem cell therapy for Alzheimer’s disease. World J Stem Cells 2020; 12(8): 787-802.
[http://dx.doi.org/10.4252/wjsc.v12.i8.787] [PMID: 32952859]
[59]
Si Z, Wang X. Stem cell therapies in Alzheimer’s disease: Applications for disease modeling. J Pharmacol Exp Ther 2021; 377(2): 207-17.
[http://dx.doi.org/10.1124/jpet.120.000324] [PMID: 33558427]
[60]
Francis PT. Glutamatergic approaches to the treatment of cognitive and behavioural symptoms of Alzheimer’s disease. Neurodegener Dis 2008; 5(3-4): 241-3.
[http://dx.doi.org/10.1159/000113713] [PMID: 18322401]
[61]
Ghosh AK, Tang J. Prospects of β-secretase inhibitors for the treatment of Alzheimer’s disease. ChemMedChem 2015; 10(9): 1463-6.
[http://dx.doi.org/10.1002/cmdc.201500216] [PMID: 26140607]
[62]
Burki T. Alzheimer’s disease research: The future of BACE inhibitors. Lancet 2018; 391(10139): 2486.
[http://dx.doi.org/10.1016/S0140-6736(18)31425-9] [PMID: 29976459]
[63]
Blume T, Filser S, Jaworska A, et al. BACE1 inhibitor MK-8931 alters formation but not stability of dendritic spines. Front Aging Neurosci 2018; 10: 229.
[http://dx.doi.org/10.3389/fnagi.2018.00229] [PMID: 30093858]
[64]
End of the BACE inhibitors? Elenbecestat trials halted amid safety concerns. Available from: https://www.alzforum.org/news/research-news/end-bace-inhibitors-elenbecestat-trials-halted-amid-safety-concerns [cited 2022 Mar 10].
[65]
Timmers M, Streffer JR, Russu A, et al. Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer’s disease: Randomized, double-blind, placebo-controlled study. Alzheimers Res Ther 2018; 10(1): 85.
[http://dx.doi.org/10.1186/s13195-018-0415-6] [PMID: 30134967]
[66]
Koriyama Y, Hori A, Ito H, et al. Discovery of atabecestat (JNJ-54861911): a thiazine-based β-amyloid precursor protein cleaving enzyme 1 inhibitor advanced to the phase 2b/3 EARLY clinical trial. J Med Chem 2021; 64(4): 1873-88.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01917] [PMID: 33588527]
[67]
Novak G, Streffer JR, Timmers M, et al. Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer’s disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study. Alzheimers Res Ther 2020; 12(1): 58.
[http://dx.doi.org/10.1186/s13195-020-00614-5] [PMID: 32410694]
[68]
Neumann U, Ufer M, Jacobson LH, et al. The BACE-1 inhibitor CNP 520 for prevention trials in Alzheimer’s disease. EMBO Mol Med 2018; 10(11): e9316.
[http://dx.doi.org/10.15252/emmm.201809316] [PMID: 30224383]
[69]
Novartis, Amgen and Banner Alzheimer’s Institute discontinue clinical program with BACE inhibitor CNP520 for Alzheimer’s prevention. Novartis. Available from: https://www.novartis.com/news/media-releases/novartis-amgen-and-banner-alzheimers-institute-discontinue-clinical-program-bace-inhibitor-cnp520-alzheimers-prevention [cited 2022 Mar 11].
[70]
Siemers E, Skinner M, Dean RA, et al. Safety, tolerability, and changes in amyloid β concentrations after administration of a γ-secretase inhibitor in volunteers. Clin Neuropharmacol 2005; 28(3): 126-32.
[http://dx.doi.org/10.1097/01.wnf.0000167360.27670.29] [PMID: 15965311]
[71]
Folch J, Petrov D, Ettcheto M, et al. Current research therapeutic strategies for Alzheimer’s disease treatment. Neural plasticity 2016. Oct;2016.
[http://dx.doi.org/10.1155/2016/8501693]
[72]
Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord 2013; 6(1): 19-33.
[http://dx.doi.org/10.1177/1756285612461679] [PMID: 23277790]
[73]
Dockens R, Wang JS, Castaneda L, et al. A placebo-controlled, multiple ascending dose study to evaluate the safety, pharmacokinetics and pharmacodynamics of avagacestat (BMS-708163) in healthy young and elderly subjects. Clin Pharmacokinet 2012; 51(10): 681-93.
[http://dx.doi.org/10.1007/s40262-012-0005-x] [PMID: 23018531]
[74]
Coric V, van Dyck CH, Salloway S, et al. Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol 2012; 69(11): 1430-40.
[http://dx.doi.org/10.1001/archneurol.2012.2194] [PMID: 22892585]
[75]
Coman H, Nemeş B. New therapeutic targets in Alzheimer’s disease. Int J Gerontol 2017; 11(1): 2-6.
[http://dx.doi.org/10.1016/j.ijge.2016.07.003]
[76]
Siopi E, Llufriu-Dabén G, Cho AH, et al. Etazolate, an α-secretase activator, reduces neuroinflammation and offers persistent neuroprotection following traumatic brain injury in mice. Neuropharmacology 2013; 67: 183-92.
[http://dx.doi.org/10.1016/j.neuropharm.2012.11.009] [PMID: 23178198]
[77]
Endres K, Fahrenholz F, Lotz J, et al. Increased CSF APPs- levels in patients with Alzheimer disease treated with acitretin. Neurology 2014; 83(21): 1930-5.
[http://dx.doi.org/10.1212/WNL.0000000000001017] [PMID: 25344383]
[78]
Bao J, Liu W, Zhou H, et al. Epigallocatechin-3-gallate alleviates cognitive deficits in APP/PS1 mice. Curr Med Sci 2020; 40(1): 18-27.
[http://dx.doi.org/10.1007/s11596-020-2142-z] [PMID: 32166661]
[79]
Ettcheto M, Cano A, Manzine PR, et al. Epigallocatechin-3-Gallate (EGCG) improves cognitive deficits aggravated by an obesogenic diet through modulation of unfolded protein response in APPswe/PS1dE9 mice. Mol Neurobiol 2020; 57(4): 1814-27.
[http://dx.doi.org/10.1007/s12035-019-01849-6] [PMID: 31838720]
[80]
Epigallocatechin gallate (EGCG). Available from: https://www.alzforum.org/therapeutics/epigallocatechin-gallate-egcg [cited 2022 Mar 12].
[81]
Wilcock GK, Black SE, Hendrix SB, Zavitz KH, Swabb EA, Laughlin MA. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer’s disease: A randomised phase II trial. Lancet Neurol 2008; 7(6): 483-93.
[http://dx.doi.org/10.1016/S1474-4422(08)70090-5] [PMID: 18450517]
[82]
Muntimadugu E, Dhommati R, Jain A, Challa VGS, Shaheen M, Khan W. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer’s disease. Eur J Pharm Sci 2016; 92: 224-34.
[http://dx.doi.org/10.1016/j.ejps.2016.05.012] [PMID: 27185298]
[83]
Hey JA, Kocis P, Hort J, et al. Discovery and identification of an endogenous metabolite of tramiprosate and its prodrug ALZ-801 that inhibits beta amyloid oligomer formation in the human brain. CNS Drugs 2018; 32(9): 849-61.
[http://dx.doi.org/10.1007/s40263-018-0554-0] [PMID: 30076539]
[84]
Aisen P, Gauthier S, Vellas B, et al. Alzhemed: A potential treatment for Alzheimer’s disease. Curr Alzheimer Res 2007; 4(4): 473-8.
[http://dx.doi.org/10.2174/156720507781788882] [PMID: 17908052]
[85]
Green Valley announces NMPA approval of oligomannate for mild to moderate Alzheimer’s disease- press release-green valley. Available from: https://www.greenvalleypharma.com/En/Index/pageView/catid/48/id/28.html [cited 2022 Mar 14].
[86]
A study of sodium oligomannate (GV-971) in participants with mild to moderate Alzheimer’s disease - full text view - Clinicaltrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT04520412 [cited 2022 Mar 18].
[87]
Wang T, Kuang W, Chen W, et al. A phase II randomized trial of sodium oligomannate in Alzheimer’s dementia. Alzheimers Res Ther 2020; 12(1): 110.
[http://dx.doi.org/10.1186/s13195-020-00678-3] [PMID: 32928279]
[88]
Szaniszlo P, German P, Hajas G, Saenz DN, Kruzel M, Boldogh I. New insights into clinical trial for colostrinin™ in Alzheimer’s disease. J Nutr Health Aging 2009; 13(3): 235-41.
[http://dx.doi.org/10.1007/s12603-009-0065-2] [PMID: 19262960]
[89]
Bilikiewicz A, Gaus W. Colostrinin1 (a naturally occurring, proline-rich, polypeptide mixture) in the treatment of Alzheimer’s disease. J Alzheimers Dis 2004; 6(1): 17-26.
[http://dx.doi.org/10.3233/JAD-2004-6103] [PMID: 15004324]
[90]
Delrieu J, Ousset PJ, Caillaud C, Vellas B. Retracted: ‘Clinical trials in Alzheimer’s disease’: Immunotherapy approaches. J Neurochem 2012; 120(s1) (Suppl. 1): 186-93.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07458.x] [PMID: 21883222]
[91]
Siemers ER, Sundell KL, Carlson C, et al. Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer’s disease patients. Alzheimers Dement 2016; 12(2): 110-20.
[http://dx.doi.org/10.1016/j.jalz.2015.06.1893] [PMID: 26238576]
[92]
Ostrowitzki S, Lasser RA, Dorflinger E, et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease. Alzheimers Res Ther 2017; 9(1): 95.
[http://dx.doi.org/10.1186/s13195-017-0318-y] [PMID: 29221491]
[93]
Klein G, Delmar P, Voyle N, et al. Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: A PET substudy interim analysis. Alzheimers Res Ther 2019; 11(1): 101.
[http://dx.doi.org/10.1186/s13195-019-0559-z] [PMID: 31831056]
[94]
Tolar M, Abushakra S, Hey JA, Porsteinsson A, Sabbagh M. Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval. Alzheimers Res Ther 2020; 12(1): 95.
[http://dx.doi.org/10.1186/s13195-020-00663-w] [PMID: 32787971]
[95]
Wilcock GK, Gauthier S, Frisoni GB, et al. Potential of low dose leuco-methylthioninium bis (hydromethanesulphonate)(LMTM) monotherapy for treatment of mild Alzheimer’s disease: Cohort analysis as modified primary outcome in a phase III clinical trial. J Alzheimers Dis 2017; 61(1): 435-57.
[http://dx.doi.org/10.3233/JAD-170560] [PMID: 29154277]
[96]
Al-Hilaly YK, Pollack SJ, Rickard JE, et al. Cysteine-independent inhibition of Alzheimer’s disease-like paired helical filament assembly by leuco-methylthioninium (LMT). J Mol Biol 2018; 430(21): 4119-31.
[http://dx.doi.org/10.1016/j.jmb.2018.08.010] [PMID: 30121297]
[97]
Safety and efficacy of TRx0237 in subjects with Alzheimer’s disease followed by open-label treatment. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03446001 [cited 2022 Apr 19]
[98]
Maurice T. Protection by sigma-1 receptor agonists is synergic with donepezil, but not with memantine, in a mouse model of amyloid-induced memory impairments. Behav Brain Res 2016; 296: 270-8.
[http://dx.doi.org/10.1016/j.bbr.2015.09.020] [PMID: 26386305]
[99]
Smith LM, Zhu R, Strittmatter SM. Disease-modifying benefit of Fyn blockade persists after washout in mouse Alzheimer’s model. Neuropharmacology 2018; 130: 54-61.
[http://dx.doi.org/10.1016/j.neuropharm.2017.11.042] [PMID: 29191754]
[100]
Toyonaga T, Smith LM, Finnema SJ, et al. In vivo synaptic density imaging with 11C-UCB-J detects treatment effects of saracatinib in a mouse model of Alzheimer disease. J Nucl Med 2019; 60(12): 1780-6.
[http://dx.doi.org/10.2967/jnumed.118.223867] [PMID: 31101744]
[101]
van Dyck CH, Nygaard HB, Chen K, et al. Effect of AZD0530 on cerebral metabolic decline in Alzheimer disease: A randomized clinical trial. JAMA Neurol 2019; 76(10): 1219-29.
[http://dx.doi.org/10.1001/jamaneurol.2019.2050] [PMID: 31329216]
[102]
Wang X, Smith K, Pearson M, et al. Early intervention of tau pathology prevents behavioral changes in the rTg4510 mouse model of tauopathy. PLoS One 2018; 13(4): e0195486.
[http://dx.doi.org/10.1371/journal.pone.0195486] [PMID: 29624602]
[103]
Barthold D, Joyce G, Wharton W, Kehoe P, Zissimopoulos J. The association of multiple anti-hypertensive medication classes with Alzheimer’s disease incidence across sex, race, and ethnicity. PLoS One 2018; 13(11): e0206705.
[http://dx.doi.org/10.1371/journal.pone.0206705] [PMID: 30383807]
[104]
Kehoe PG. The coming of age of the angiotensin hypothesis in Alzheimer’s disease: progress toward disease prevention and treatment? J Alzheimers Dis 2018; 62(3): 1443-66.
[http://dx.doi.org/10.3233/JAD-171119] [PMID: 29562545]
[105]
Telmisartan: Severe angioedema of laryngeal inlet: case report. React Wkly 2018; 1705(1): 297-7. Available from: https://www.alzforum.org/therapeutics/telmisartan [cited 2022 Apr 28]
[106]
Haditsch U, Roth T, Rodriguez L, et al. Alzheimer’s disease-like neurodegeneration in Porphyromonas gingivalis infected neurons with persistent expression of active gingipains. J Alzheimers Dis 2020; 75(4): 1361-76.
[http://dx.doi.org/10.3233/JAD-200393] [PMID: 32390638]
[107]
Raha D, Broce S, Haditsch U, et al. COR388, a novel gingipain inhibitor, decreases fragmentation of APOE in the central nervous system of Alzheimer’s disease patients. Alzheimers Dement 2020; 16(S9): e040578.
[http://dx.doi.org/10.1002/alz.040578]
[108]
Available from: https://www.alzheimers.gov/alzheimers/clinical- trials/gain-trialcor388-alzheimers-disease [cited 2022 May 2].
[109]
Atuzaginstat Available from: https://www.alzforum.org/therapeutics/atuzaginstat [cited 2022 May 2].

Rights & Permissions Print Cite
Article Metrics
37
2
Wayfinder Image
World Suicide Prevention Day
© 2024 Bentham Science Publishers | Privacy Policy