Antony Justin, Chennu Manisha, Tenzin Choephel, Peet Thomas, Victoria, Jeyarani, Sayani Banerjee, Sunil Mani
Antony Justin, Chennu Manisha, Tenzin Choephel, Peet Thomas, Victoria, Jeyarani, Sayani Banerjee, Sunil Mani
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.
Volume - 13,
Issue - 4,
Year - 2020
Alzheimer’s disease (AD) is a chronic, slowly progressive neurodegenerative disorder and most common in elderly patients. According to World Health Organization (WHO) report 2016, about 44 million people are affected with Alzheimer’s disease (AD) worldwide. Currently, FDA approved treatment for AD is merely providing symptomatic relief rather than complete cure. The fact that AD responsible for almost 70% of dementia, it is enough to depict the depth of the situation. Hence, this brought to the new investigations respect to novel array of therapeutic options like immunotherapeutic approach for AD. Primarily it involves two approaches, namely; active immunotherapy and passive immunotherapy. Active immunotherapy approach involves the administration of antigen in order to stimulate the activation of release of antibodies. The passive immunotherapy is based on the use of antibodies directed to the C-terminus, N-terminus as well as the mid-domain of Amyloid ß peptide. Although these approaches seem to be a solution to the current therapeutic barriers, the applicability of immunotherapeutic approaches in practical scenario is far from being full filled mainly because of the numerous challenges faced. The immune reactions like meningoencephalitis, the very low penetrability of antibodies into the Blood-Brain Barrier (BBB) and lack of effective animal models pose biggest demerits. The current review investigates details of the history of clinical trials and the details of ongoing and promising trials in the field of immunotherapy for AD.
Cite this article:
Antony Justin, Chennu Manisha, Tenzin Choephel, Peet Thomas, Victoria, Jeyarani, Sayani Banerjee, Sunil Mani. Recent advances in the treatment of Alzheimer’s disease: An Immunotherapeutic approach. Research J. Pharm. and Tech 2020; 13(4):2057-2062. doi: 10.5958/0974-360X.2020.00370.4
Antony Justin, Chennu Manisha, Tenzin Choephel, Peet Thomas, Victoria, Jeyarani, Sayani Banerjee, Sunil Mani. Recent advances in the treatment of Alzheimer’s disease: An Immunotherapeutic approach. Research J. Pharm. and Tech 2020; 13(4):2057-2062. doi: 10.5958/0974-360X.2020.00370.4 Available on: https://rjptonline.org/AbstractView.aspx?PID=2020-13-4-80
1. M.VijeyAanandhi, Niventhi.A, Rujaswini.T, Hemalatha C.N, Praveen.D. A Comprehensive Review on the Role of Tau Proteins in Alzheimer’s Pathology. Research J. Pharm. and Tech 2018; 11(2):788-790.
2. Vasudev Pai, C. S Shreedhara, Chandrashekar K. S, Aravinda Pai, Venkatesh Kamath. Cognitive Enhancement and Neuroprotective Effects of Ancient Ayurvedic Medicinal Plant Celastrus Paniculatus: An Overview. Research J. Pharm. and Tech 2016; 9(8):1295-1298.
3. Peet Thomas, S Victoria Jeyarani, Tenzin Choephel, Chennu Manisha, Justin Antony. Recent Plant Based Remedies for Alzheimer’s Disease, Parkinson’s Disease and Cerebral Ischemic Stroke. Research J. Pharm. and Tech 2019; 12(8): 3951-3959.
4. Alzheimer's disease [Internet]. Alzheimer's Society. 2018 [cited 31 July 2018]. Available from: https://www.alzheimers.org.uk/about-dementia/types-dementia/alzheimers-disease
5. Dementia [Internet]. World Health Organization. 2018 [cited 31 July 2018]. Available from: http://www.who.int/news-room/fact-sheets/detail/dementia
6. Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M. World Alzheimer Report 2016 Improving healthcare for people living with dementia Coverage, Quality And Costs Now And In The Future [Internet]. London: Alzheimer’s Disease International; 2016 [cited 31 July 2018]. Available from: https://www.alz.co.uk/research/WorldAlzheimerReport2016.pdf
7. Martins R, Villemagne V, Sohrabi H, Chatterjee P, Shah T, VerdileG et al. Alzheimer’s Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies—Gains from AIBL and DIAN Cohort Studies. Journal of Alzheimer's Disease. 2018;62(3):965-992.
8. Radha Mahendran, SuganyaJeyabasker, Astral Francis, Sharanya Manoharan. Homology Modeling and in silico docking analysis of BDNF in the treatment of Alzheimer’s disease. Research J. Pharm. and Tech. 2017; 10(9): 2899-2906.
9. Lanctôt K, Amatniek J, Ancoli-Israel S, Arnold S, Ballard C, Cohen-Mansfield J et al. Neuropsychiatric signs and symptoms of Alzheimer's disease: New treatment paradigms. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2017;3(3):440-449.
10. Hampel H, Toschi N, Babiloni C, Baldacci F, Black K, Bokde A et al. Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology. Journal of Alzheimer's Disease. 2018;64(s1):S47-S105.
11. Chen R, Chan P, Chu H, Lin Y, Chang P, Chen C et al. Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta-analysis. PLOS ONE. 2017;12(8):e0183586.
12. V. Chitra, J. Narayanan. In vitro Screening for Anti-Cholinesterase and Anti Oxidant Activity of Extract of Garcinia hanburyi. Research J. Pharm. and Tech 2018; 11(7): 2918-2921.
13. Vivek Kumar Sharma. Current Therapeutic Strategies for Alzheimer’s disease: A Lost Direction or A Hope Remains?. Research J. Pharmacology and Pharmacodynamics. 2010; 2(3): 215-220.
14. Sowmya Hari, S. Akilashree. In Silico Homology Modeling of Presenilin 2- Therapeutic Target for Alzheimer’s disease. Research J. Pharm. and Tech. 2019; 12(7):3405-3409.
15. Jindal H, Bhatt B, SK S, Malik J. Alzheimer disease immunotherapeutics: Then and now. Human vaccines &immunotherapeutics. 2014;10(9).
16. Castellani R, Rolston R, Smith M. Alzheimer Disease. Disease-a-Month. 2010;56(9):484-546.
17. M.VijeyAanandhi, Niventhi.A, Rujaswini.T, Hemalatha C.N, Praveen.D. A Comprehensive Review on the Role of Tau Proteins in Alzheimer’s Pathology. Research J. Pharm. and Tech 2018; 11(2):788-790.
18. Iqbal K, Liu F, Gong C. Alzheimer disease therapeutics: Focus on the disease and not just plaques and tangles. Biochemical Pharmacology. 2014;88(4):631-639.
19. Huang Y, Mucke L. Alzheimer Mechanisms and Therapeutic Strategies. Cell. 2012;148(6):1204-1222.
20. NevedaBaskeran. Iron Deficiency and Brain Disorders. Research J. Pharm. and Tech. 7(3): Mar., 2014; Page 352-353.
21. Matsumoto Y, Kohyama K. Alzheimer’s disease and immunotherapy: what is wrong with clinical trials?. ImmunoTargets and Therapy. 2015;:27.
22. Barrera-Ocampo A, Lopera F. Amyloid-beta immunotherapy: the hope for Alzheimer disease? Colomb Med (Cali). 47(4):203–12.
23. Fu HJ, Liu B, Frost JL, Lemere CA. Amyloid-β Immunotherapy for Alzheimer’s Disease. CNS NeurolDisord Drug Targets. 2010 Apr;9(2):197–206.
24. Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-β immunotherapy? Nat Rev Neurol. 2010 Feb;6(2):108–19.
25. Karthik Dhananjayan, Arunachalam Sumathy, SivanandyPalanisamy. Molecular Docking Studies and in-vitro Acetylcholinesterase Inhibition by Terpenoids and Flavonoids. Asian J. Research Chem. 6(11): November 2013; Page 1011-1017.
26. Weller RO, Preston SD, Subash M, Carare RO. Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer disease. Alzheimers Res Ther. 2009 Oct 12;1(2):6.
27. Wisniewski T, Goñi F. Immunotherapeutic Approaches for Alzheimer’s Disease. Neuron. 2015 Mar 18;85(6):1162–76.
28. Lemere CA. Immunotherapy for Alzheimer’s disease: hoops and hurdles. MolNeurodegener. 2013 Oct 22;8:36.
29. Schaeffer EL, Figueiró M, Gattaz WF. Insights into Alzheimer disease pathogenesis from studies in transgenic animal models. Clinics (Sao Paulo). 2011 Jun;66(Suppl 1):45–54.
30. Serrano-Pozo A, Qian J, Monsell SE, Blacker D, Gómez-lsla T, Betensky RA, et al. Mild to Moderate Alzheimer Dementia with Insufficient Neuropathological Changes. Ann Neurol. 2014 Apr;75(4):597–601.
31. Radha Mahendran, SuganyaJeyabasker, Astral Francis, Sharanya Manoharan. Homology Modeling and in silico docking analysis of BDNF in the treatment of Alzheimer’s disease. Research J. Pharm. and Tech. 2017; 10(9): 2899-2906.
32. Senthil Venkatachalam, Ayush Jaiswal, Anindita De, Rohith Krishnan Vijayakumar. Repurposing Drugs for Management of Alzheimer Disease. Research J. Pharm. and Tech. 2019; 12(6):3078-3088.
33. SreeLekshmi. R. S, P. Shanmugasundaram. Neuroprotective Properties of Statins. Research J. Pharm. and Tech 2018; 11(8): 3581-3584.
34. Savitha P., Saravana Kumar S.2. Effect of Omega-3 Fatty acids on Memory – Review. Research J. Pharm. and Tech. 7(6): June, 2014; Page 715-718.
35. V. Chitra, J. Narayanan. In vitro Screening for Anti-Cholinesterase and Anti Oxidant Activity of Extract of Garcinia hanburyi. Research J. Pharm. and Tech 2018; 11(7): 2918-2921.
36. Lakshmi. K, Karishma. S k, N.S.S. Chandra Sekhar. G, Narendra Babu. A, Bhargav Kumar. N. Terminalia chebula Retz improve memory and learning in Alzheimer’s Model: (Experimental Study in Rat). Research J. Pharm. and Tech 2018; 11(11): 4888-4891.
37. Gouras GK. Immunotherapy for Alzheimer disease. MAbs. 2009;1(2):112–4.
38. Morgan D. Immunotherapy for Alzheimer’s Disease. J Intern Med. 2011 Jan;269(1):54–63.
39. Lambracht-Washington D, Rosenberg RN. Anti-amyloid-beta to tau-based immunization: developments in immunotherapy for Alzheimer’s disease. ImmunotargetsTher. 2013 Aug 10;2:105–14.
40. Wilcock DM, Colton CA. Anti-Aß immunotherapy in Alzheimer’s disease; relevance of transgenic mouse studies to clinical trials. J Alzheimers Dis. 2008 Dec;15(4):555–69.
41. Cynis H, Frost JL, Crehan H, Lemere CA. Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges. MolNeurodegener [Internet]. 2016 Jun 30 [cited 2018 Jun 22];11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929720/
42. Lambracht-Washington D, Rosenberg R. Active DNA Aβ42 vaccination as immunotherapy for Alzheimer disease. Translational Neuroscience. 2012;3(4).
43. Giménez-Llort L, Rivera-Hernández G, Marín-Argany M, Sánchez-Quesada JL, Villegas S. Early intervention in the 3xTg-AD mice with an amyloid β-antibody fragment ameliorates first hallmarks of Alzheimer disease. MAbs. 2013 Sep 1;5(5):665–864.
44. Sigurdsson EM. Tau-Focused Immunotherapy for Alzheimer’s Disease and Related Tauopathies. Curr Alzheimer Res. 2009 Oct;6(5):446–50.
45. d’Abramo C, Acker CM, Jimenez HT, Davies P. Tau Passive Immunotherapy in Mutant P301L Mice: Antibody Affinity versus Specificity. PLoS One [Internet]. 2013 Apr 29 [cited 2018 Jun 22];8(4). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639259/
46. Lannfelt L, Möller C, Basun H, Osswald G, Sehlin D, Satlin A, et al. Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer’s disease. Alzheimers Res Ther. 2014 Mar 24;6(2):16.
47. Frost JL, Liu B, Kleinschmidt M, Schilling S, Demuth H-U, Lemere CA. Passive Immunization against Pyroglutamate-3 Amyloid-β Reduces Plaque Burden in Alzheimer-Like Transgenic Mice: A Pilot Study. Neurodegener Dis. 2012 Apr;10(1–4):265–70.
48. Chai X, Wu S, Murray TK, Kinley R, Cella CV, Sims H, et al. Passive Immunization with Anti-Tau Antibodies in Two Transgenic Models. J Biol Chem. 2011 Sep 30;286(39):34457–67.
49. Lannfelt L, Relkin NR, Siemers ER. Amyloid-ß-directed immunotherapy for Alzheimer’s disease. J Intern Med. 2014 Mar;275(3):284–95.
50. Rasool S, Martinez-Coria H, Wu JW, LaFerla F, Glabe CG. Systemic vaccination with anti-oligomeric monoclonal antibodies improves cognitive function by reducing Aβ deposition and tau pathology in 3xTg-AD mice. J Neurochem. 2013 Aug;126(4):473–82.
51. Spires-Jones TL, Mielke M, Rozkalne A, Meyer-Luehmann M, de Calignon A, Bacskai BJ, et al. Passive immunotherapy rapidly increases structural plasticity in a mouse model of Alzheimer disease. Neurobiol Dis. 2009 Feb;33(2):213–20.
52. M. VijeyAanandhi, Yeshwanth Prasanna Kumar. B, Ranadheer Chowdary. P, Praveen. D. A Review on the Role of Presenilin in Alzheimer’s Disease . Research J. Pharm. and Tech 2018; 11(5):2149-2151.