RECENT ADVANCES INPHARMACOTHERAPY OF ALZHEIMER’S DISEASE
DOI:
https://doi.org/10.22159/ijcpr.2021v13i6.1916Keywords:
Alzheimer's disease (AD), β-amyloid (Aβ), Tau proteins, Recent advanceAbstract
The management of Alzheimer's disease (AD) has been a long-standing challenge and area of interest. Advances in knowledge of the pathogenesis of disease and an increase in disease burden have prompted investigation into innovative therapeutics over the last two decades. Current approved therapies are symptomatic treatments having some effect on cognitive function. Therapies that target β-amyloid (Aβ) have been the focus of efforts to develop a disease modification treatment for AD but these approaches have failed to show any clinical benefit so far. Beyond the 'Aβ hypothesis', there are a number of newer approaches to treat AD. This short review will summarize approved drug therapies, recent clinical trials and new approaches for the treatment of AD.
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References
Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001;81(2):741-66. doi: 10.1152/physrev. 2001.81.2.741, PMID 11274343.
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010;362(4):329-44. doi: 10.1056/NEJMra0909142, PMID 20107219.
Mayeux R. Clinical practice. Early Alzheimer’s disease. N Engl J Med. 2010;362(23):2194-201. doi: 10.1056/NEJMcp0910236, PMID 20558370.
Brookmeyer R, Johnson E, Ziegler Graham K, Arrighi HM. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement. 2007;3(3):186-91. doi: 10.1016/j.jalz.2007.04.381, PMID 19595937.
Braak H, Braak E. Neuropathologicalstageing of alzheimer-relatedchanges. Acta Neuropathol. 1991;82(4):239-59. doi: 10.1007/BF00308809.
Hyman BT, Trojanowski JQ. Editorial on consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol. 1997;56(10):1095-7. doi: 10.1097/00005072-199710000-00002.
Aprahamian I, Stella F, Forlenza OV. New treatment strategies for Alzheimer’s disease: is there a hope? Indian J Med Res. 2013;138(4):449-60. PMID 24434253.
Bolognesi ML, Bartolini M, Tarozzi A, Morroni F, Lizzi F, Milelli A, Minarini A, Rosini M, Hrelia P, Andrisano V, Melchiorre C. Multitargeted drugs discovery: balancing anti-amyloid and anticholinesterase capacity in a single chemical entity. Bioorg Med Chem Lett. 2011;21(9):2655-8. doi: 10.1016/ j.bmcl.2010.12.093, PMID 21236667.
Nagaraja Prasad S, Jagadeesh K, Vedavathi H, Shreenivas P. Alzheimer disease: therapeutic targets and recent developments in treatment. SchAcad J Pharm. 2015;4:222-5.
Wiessner C, Wiederhold KH, Tissot AC, Frey P, Danner S, Jacobson LH, Jennings GT, Luond R, Ortmann R, Reichwald J, Zurini M, Mir A, Bachmann MF, Staufenbiel M. The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. J Neurosci. 2011;31(25):9323-31. doi: 10.1523/JNEUROSCI.0293-11.2011, PMID 21697382.
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):504-17. doi: 10.1111/j.1365-2125.2011.04134.x, PMID 22035455.
Panza F, Frisardi V, Imbimbo BP, Seripa D, Paris F, Santamato A. Anti-β-amyloid immunotherapy for Alzheimer’s disease: focus. Colomb Med (Cali). 2016;47(4):203–12. PMID: 28293044.
Zhao B, Yu M, Neitzel M, Marugg J, Jagodzinski J, Lee M, Hu K, Schenk D, Yednock T, Basi G. Identification of γ-secretase inhibitor potency determinants on presenilin. J Biol Chem. 2008;283(5):2927-38. doi: 10.1074/jbc.M708870200, PMID 18032377.
Tariot P, Sabbagh M, Flitman S, Reyes P, Taber L, Seely L. P1-254: A safety, tolerability and pharmacokinetic study of dimebon in patients with Alzheimer’s disease already receiving donepezil. Alzheimers Dem. 2009;5(4S_Part_8):251. doi: 10.1016/j.jalz.2009.04.262.
Jia Q, Deng Y, Qing H. Potential therapeutic strategies for Alzheimer’s disease targeting or beyond β-amyloid: insights from clinical trials. Biomed Res Int. 2014;2014:837157. doi: 10.1155/2014/837157. PMID 25136630.
Sereno L, Coma M, Rodriguez M, Sanchez-Ferrer P, Sanchez MB, Gich I, Agullo JM, Perez M, Avila J, Guardia Laguarta C, Clarimon J, Lleo A, Gomez-Isla T. A novel GSK-3beta inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol Dis. 2009;35(3):359-67. doi: 10.1016/ j.nbd.2009.05.025, PMID 19523516.
Craft S. The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol. 2009;66(3):300-5. doi: 10.1001/archneurol.2009.27, PMID 19273747.
Nordberg A, Darreh-Shori T, Svenson A, Guan Z. AChE and BuChE activities in CSF of mild AD patients following 12 mo of rivastigmine treatment. J Neurol Sci. 2001;187:0144.
Nikolic WV, Bai Y, Obregon D, Hou H, Mori T, Zeng J, Ehrhart J, Shytle RD, Giunta B, Morgan D, Town T, Tan J. Transcutaneous beta-amyloid immunization reduces cerebral beta-amyloid deposits without T cell infiltration and microhemorrhage. Proc Natl Acad Sci USA. 2007;104(7):2507-12. doi: 10.1073/ pnas.0609377104, PMID 17264212.
Wang T, Wang CY, Shan ZY, Teng WP, Wang ZY. Clioquinol reduces zinc accumulation in neuritic plaques and inhibits the amyloidogenic pathway in AβPP/PS1 transgenic mouse brain. J Alzheimers Dis. 2012;29(3):549-59. doi: 10.3233/JAD-2011-111874, PMID 22269164.
Huang TC, Lu KT, Wo YY, Wu YJ, Yang YL. Resveratrol protects rats from Aβ-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation. Plos One. 2011;6(12):e29102. doi: 10.1371/journal.pone.0029102, PMID 22220203.
Graham AJ, Martin Ruiz CM, Teaktong T, Ray MA, Court JA. Human brain nicotinic receptors, their distribution and participation in neuropsychiatric disorders. Curr Drug Targets CNS Neurol Disord. 2002;1(4):387-97. doi: 10.2174/ 1568007023339283, PMID 12769611.
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