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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Review Article

Current and Future of Alzheimer's Therapy with the Best Approach

Author(s): Harminder Singh, Viney Chawla*, Ritu Bala and Harish Dureja

Volume 19, Issue 9, 2020

Page: [691 - 697] Pages: 7

DOI: 10.2174/1871527319666200430000538

Price: $65

Abstract

Introduction: In spite of the steady progress in the understanding of the etiopathogenesis of Alzheimer's Disease (AD) for the last 50 years, exceptionally few long-standing drugs are, at present, used for AD therapy. New interventions that either prevent, slow or stop the disease are urgently warranted to overcome the growing AD burden. The aim of this narrative review is to summarize the currently existing preclinical and clinical evidence regarding new drug development and biomarkers for better understanding and focused management of AD. This article reviews the various potential and existing targets /receptors with valid biomarkers applied in recent years to address the early-stage tasks of the AD drug discovery process. A comprehensive literature search was conducted in the relevant databases to identify studies published in recent years. In conclusion, the new approaches seem to aim at examining the prospective neuroprotective activity of disease-modifying drugs in the presymptomatic phases of AD, using biomarkers that detect progression of the disease before the growth of overt dementia.

Keywords: Alzheimer’s disease, neuro-inflammation, immunoglobulins, monoclonal antibodies, peripheral metabolic deregulation, immunotherapy

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[1]
Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers 2015; 1: 15056.
[http://dx.doi.org/10.1038/nrdp.2015.56] [PMID: 27188934]
[2]
Scheltens P, Blennow K, Breteler MM, et al. Alzheimer’s disease. Lancet 2016; 388(10043): 505-17.
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[3]
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 2007; 3(3): 186-91.
[http://dx.doi.org/10.1016/j.jalz.2007.04.381] [PMID: 19595937]
[4]
Hodes JF, Oakley CI, O’Keefe JH, et al. Alzheimer’s prevention versus risk reduction: transcending semantics for clinical practice. Front Neurol 2019; 9: 1179.
[http://dx.doi.org/10.3389/fneur.2018.01179] [PMID: 30719021]
[5]
Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement 2017; 13: 325-73.
[http://dx.doi.org/10.1016/j.jalz.2017.02.001]
[6]
Ferri CP, Prince M, Brayne C, et al. Alzheimer’s Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366(9503): 2112-7.
[http://dx.doi.org/10.1016/S0140-6736(05)67889-0] [PMID: 16360788]
[7]
Crous-Bou M, Minguillón C, Gramunt N, Molinuevo JL. Alzheimer’s disease prevention: from risk factors to early intervention. Alzheimers Res Ther 2017; 9(1): 71.
[http://dx.doi.org/10.1186/s13195-017-0297-z] [PMID: 28899416]
[8]
Farlow M. A clinical overview of cholinesterase inhibitors in Alzheimer’s disease. Int Psychogeriatr 2002; 14(S1)(Suppl. 1): 93-126.
[http://dx.doi.org/10.1017/S1041610203008688] [PMID: 12636182]
[9]
Cummings JL, Morstorf T, Zhong K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther 2014; 6(4): 37.
[http://dx.doi.org/10.1186/alzrt269] [PMID: 25024750]
[10]
Singh A, Hasan A, Tiwari S, Pandey LM. Therapeutic advancement in Alzheimer disease: new hopes on the horizon? CNS Neurol Disord Drug Targets 2018; 17(8): 571-89.
[http://dx.doi.org/10.2174/1871527317666180627122448] [PMID: 29952273]
[11]
Park J, Wetzel I, Marriott I, et al. A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease. Nat Neurosci 2018; 21(7): 941-51.
[http://dx.doi.org/10.1038/s41593-018-0175-4] [PMID: 29950669]
[12]
Hong S, Beja-Glasser VF, Nfonoyim BM, et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 2016; 352(6286): 712-6.
[http://dx.doi.org/10.1126/science.aad8373] [PMID: 27033548]
[13]
Katsel P, Tan W, Haroutunian V. Gain in brain immunity in the oldest-old differentiates cognitively normal from demented individuals. PLoS One 2009; 4(10)e7642
[http://dx.doi.org/10.1371/journal.pone.0007642] [PMID: 19865478]
[14]
Wilcock DM. A changing perspective on the role of neuroinflammation in Alzheimer’s disease. Int J Alzheimers Dis 2012; 2012495243
[http://dx.doi.org/10.1155/2012/495243] [PMID: 22844636]
[15]
De Felice FG. Alzheimer’s disease and insulin resistance: translating basic science into clinical applications. J Clin Invest 2013; 123(2): 531-9.
[http://dx.doi.org/10.1172/JCI64595] [PMID: 23485579]
[16]
De Felice FG, Ferreira ST. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease. Diabetes 2014; 63(7): 2262-72.
[http://dx.doi.org/10.2337/db13-1954] [PMID: 24931033]
[17]
Rabins PV, Rovner BW, Rummans T, Schneider LS, Tariot PN. Guideline watch (October 2014): practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. 2014. Available from: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/alzheimerwatch.
[18]
Hort J, O’Brien JT, Gainotti G, et al. EFNS scientist panelon dementia EFNS guidelines for the diagnosisand management of Alzheimer’s disease. Eur J Neurol 2010; 17: 1236-48.
[19]
Doody RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001; 56(9): 1154-66.
[http://dx.doi.org/10.1212/WNL.56.9.1154] [PMID: 11342679]
[20]
Grossberg GT, Manes F, Allegri RF, et al. The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer’s disease taking cholinesterase inhibitors. CNS Drugs 2013; 27(6): 469-78.
[http://dx.doi.org/10.1007/s40263-013-0077-7] [PMID: 23733403]
[21]
Littlejohns TJ, Henley WE, Lang IA, et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology 2014; 83(10): 920-8.
[http://dx.doi.org/10.1212/WNL.0000000000000755] [PMID: 25098535]
[22]
Gupta PP, Pandey RD, Jha D, Shrivastav V, Kumar S. Role of traditional nonsteroidal anti-inflammatory drugs in Alzheimer’s disease: a meta-analysis of randomized clinical trials. Am J Alzheimers Dis Other Demen 2015; 30(2): 178-82.
[http://dx.doi.org/10.1177/1533317514542644] [PMID: 25024454]
[23]
Lee LK, Shahar S, Chin AV, Yusoff NA. Docosahexaenoic acid-concentrated fish oil supplementation in subjects with Mild Cognitive Impairment (MCI): a 12-month randomised, double-blind, placebo-controlled trial. Psychopharmacology (Berl) 2013; 225(3): 605-12.
[http://dx.doi.org/10.1007/s00213-012-2848-0] [PMID: 22932777]
[24]
Bo Y, Zhang X, Wang Y, et al. The n-3 polyunsaturated fatty acids supplementation improved the cognitive function in the Chinese elderly with mild cognitive impairment: A double-blind randomized controlled trial. Nutrients 2017; 9(1)E54
[http://dx.doi.org/10.3390/nu9010054] [PMID: 28075381]
[25]
Zec RF, Burkett NR. Non-pharmacological and pharmacological treatment of the cognitive and behavioral symptoms of Alzheimer disease. NeuroRehabilitation 2008; 23(5): 425-38.
[http://dx.doi.org/10.3233/NRE-2008-23506] [PMID: 18957729]
[26]
Ballard C, Corbett A, Chitramohan R, Aarsland D. Management of agitation and aggression associated with Alzheimer’s disease: controversies and possible solutions. Curr Opin Psychiatry 2009; 22(6): 532-40.
[http://dx.doi.org/10.1097/YCO.0b013e32833111f9] [PMID: 19696673]
[27]
Bateman RJ, Xiong C, Benzinger TL, et al. Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012; 367(9): 795-804.
[http://dx.doi.org/10.1056/NEJMoa1202753] [PMID: 22784036]
[28]
Pooler AM, Polydoro M, Wegmann S, Nicholls SB, Spires-Jones TL, Hyman BT. Propagation of tau pathology in Alzheimer’s disease: identification of novel therapeutic targets. Alzheimers Res Ther 2013; 5(5): 49.
[http://dx.doi.org/10.1186/alzrt214] [PMID: 24152385]
[29]
Panza F, Lozupone M, Logroscino G, Imbimbo BP. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat Rev Neurol 2019; 15(2): 73-88.
[http://dx.doi.org/10.1038/s41582-018-0116-6] [PMID: 30610216]
[30]
Waite LM. Treatment for Alzheimer’s disease: has anything changed? Aust Prescr 2015; 38(2): 60-3.
[http://dx.doi.org/10.18773/austprescr.2015.018] [PMID: 26648618]
[31]
Evin G, Hince C. BACE1 as a therapeutic target in Alzheimer’s disease: rationale and current status. Drugs Aging 2013; 30(10): 755-64.
[http://dx.doi.org/10.1007/s40266-013-0099-3] [PMID: 23842796]
[32]
Kennedy ME, Stamford AW, Chen X, et al. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients. Sci Transl Med 2016; 8(363)363ra150
[http://dx.doi.org/10.1126/scitranslmed.aad9704] [PMID: 27807285]
[33]
Ahmad SS, Khan S, Kamal MA, Wasi U. The structure and function of α, β andγ-Secretase as therapeutic target enzymes into the development of Alzheimer’s disease: A review. CNS Neurol Disord Drug Targets 2019; 18(9): 657-67.
[http://dx.doi.org/10.2174/1871527318666191011145941] [PMID: 31608840]
[34]
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]
[35]
Salloway S, Sperling R, Fox NC, et al. Bapineuzumab 301 and 302 clinical trial investigators. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 2014; 370(4): 322-33.
[http://dx.doi.org/10.1056/NEJMoa1304839] [PMID: 24450891]
[36]
Doody RS, Thomas RG, Farlow M, et al. Alzheimer’s Disease Cooperative Study Steering Committee. Solanezumab Study Group. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 2014; 370(4): 311-21.
[http://dx.doi.org/10.1056/NEJMoa1312889] [PMID: 24450890]
[37]
McGuinness B, O’Hare J, Craig D, Bullock R, Malouf R, Passmore P. Statins for the treatment of dementia. Cochrane Database Syst Rev 2010; 4(8)CD007514
[PMID: 20687089]
[38]
Griffin WST. Perispinal etanercept: potential as an Alzheimer therapeutic. J Neuroinflammation 2008; 5: 3.
[http://dx.doi.org/10.1186/1742-2094-5-3] [PMID: 18186919]
[39]
Park J, Lee SY, Shon J, et al. Adalimumab improves cognitive impairment, exerts neuroprotective effects and attenuates neuroinflammation in an Aβ1-40-injected mouse model of Alzheimer’s disease. Cytotherapy 2019; 21(6): 671-82.
[http://dx.doi.org/10.1016/j.jcyt.2019.04.054] [PMID: 31076196]
[40]
Wisniewski T, Konietzko U. Amyloid-β immunisation for Alzheimer’s disease. Lancet Neurol 2008; 7(9): 805-11.
[http://dx.doi.org/10.1016/S1474-4422(08)70170-4] [PMID: 18667360]
[41]
Gilman S, Koller M, Black RS, et al. AN1792(QS-21)-201 Study Team. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005; 64(9): 1553-62.
[http://dx.doi.org/10.1212/01.WNL.0000159740.16984.3C] [PMID: 15883316]
[42]
Pedersen JT, Sigurdsson EM. Tau immunotherapy for Alzheimer’s disease. Trends Mol Med 2015; 21(6): 394-402.
[http://dx.doi.org/10.1016/j.molmed.2015.03.003] [PMID: 25846560]
[43]
Rosenmann H. Immunotherapy for targeting tau pathology in Alzheimer’s disease and tauopathies. Curr Alzheimer Res 2013; 10(3): 217-28.
[http://dx.doi.org/10.2174/1567205011310030001] [PMID: 23534533]
[44]
Novak P, Schmidt R, Kontsekova E, et al. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol 2017; 16(2): 123-34.
[http://dx.doi.org/10.1016/S1474-4422(16)30331-3] [PMID: 27955995]
[45]
Ali F, Siddique YH. Bioavailability and pharmaco-therapeutic potential of Luteolin in overcoming Alzheimer’s disease. CNS Neurol Disord Drug Targets 2019; 18(5): 352-65.
[http://dx.doi.org/10.2174/1871527318666190319141835] [PMID: 30892166]
[46]
Miri AL, Hosni AP, Gomes JC, et al. Marcano RG, da S Pereira MC, Kerppers II. Study of the effects of L-tryptophane nanoparticles on motor behavior in Alzheimer’s experimental models. CNS Neurol Disord Drug Targets 2019; 18(1): 44-51.
[http://dx.doi.org/10.2174/1871527317666181105111157] [PMID: 30394223]
[47]
Gupta S, Singhal NK, Ganesh S, Sandhir R. Extending arms of insulin resistance from diabetes to Alzheimer’s disease: identification of potential therapeutic targets. CNS Neurol Disord Drug Targets 2019; 18(3): 172-84.
[http://dx.doi.org/10.2174/1871527317666181114163515] [PMID: 30430949]
[48]
Shi Y, Wang Y, Wei H. Dantrolene: From malignant hyperthermia to Alzheimer’s disease. CNS Neurol Disord Drug Targets 2019; 18(9): 668-76.
[http://dx.doi.org/10.2174/1871527317666180619162649] [PMID: 29921212]
[49]
Wang K, Sun W, Zhang L, et al. Oleanolic acid ameliorates Aβ25-35 injection-induced memory deficit in Alzheimer’s disease model rats by maintaining synaptic plasticity. CNS Neurol Disord Drug Targets 2018; 17(5): 389-99.
[http://dx.doi.org/10.2174/1871527317666180525113109] [PMID: 29793416]
[50]
Beg T, Jyoti S, Naz F, et al. Protective effect of kaempferol on the transgenic drosophila model of Alzheimer’s disease. CNS Neurol Disord Drug Targets 2018; 17(6): 421-9.
[http://dx.doi.org/10.2174/1871527317666180508123050] [PMID: 29745345]
[51]
Bais S, Kumari R, Prashar Y. Ameliorative effect of trans-sinapic acid and its protective role in cerebral hypoxia in aluminium chloride induced dementia of Alzheimer’s Type. CNS Neurol Disord Drug Targets 2018; 17(2): 144-54.
[http://dx.doi.org/10.2174/1871527317666180309130912] [PMID: 29521253]
[52]
Zvěřová M. Alzheimer’s disease and blood-based biomarkers - potential contexts of use. Neuropsychiatr Dis Treat 2018; 14: 1877-82.
[http://dx.doi.org/10.2147/NDT.S172285] [PMID: 30050302]

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