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MINI-REVIEW

Innovative approaches and challenges in antibody-based therapeutics for Alzheimer’s disease

Tolulope Judah Gbayisomore1,2* ,  Kingsley Afoke Iteire2 ,  Inibehe Ime Okon3 ,  Isunu Lucky Efe4 ,  Okikiola Oyindamola Falua5 ,  Waliullahi Odebode Opeyemi1 ,  Alex Sorlelodum Gideon6 ,  Rufus Oluwagbemileke Ajayi7 ,  Abdul-Hanan Saani Inusah8
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1 Data Intelligence and Scientific Innovation Unit, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria
2 Department of Anatomy, Faculty of Basic Medical Sciences, University of Medical Sciences, Ondo City, Ondo State, Nigeria
3 Department of Research, Medical Research Circle (MedReC), Bukavu, South Kivu, Democratic Republic of the Congo
4 Department of Microbiology, Faculty of Sciences, Federal University of Technology, Akure, Ondo State, Nigeria
5 Department of Biochemistry, Faculty of Basic medical sciences, Olabisi Onabanjo University, Ago-Iwoye, Ogun State, Nigeria
6 Department of Anatomy, University of Port Harcourt, Port Harcourt, Rivers State, Nigeria
7 Department of Public Health, University of Illinois Springfield, Illinois, United states of America
8 Department of Public Health, School of Medicine, University for Development Studies, Tamale, Ghana
INNOSC Theranostics and Pharmacological Sciences 2024, 7(3), 2953 https://doi.org/10.36922/itps.2953
Submitted: 16 February 2024 | Accepted: 28 March 2024 | Published: 30 April 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Neurological conditions, such as Alzheimer’s disease (AD) and tau-related pathologies, represent a substantial worldwide health dilemma. This review explores recent advancements and challenges in single-domain antibody (VHH)-based strategies targeting beta-secretase 1 (BACE1) inhibition and tau-related therapeutics. The methodology adopted in this study involved a comprehensive search of databases (e.g., Scopus, PubMed, and Google Scholar), with recent articles cited to provide an up-to-date overview. The research examines the limitations of current AD treatments, emphasizing the need for innovative techniques. We, further, discuss potential gene transfer methods using adeno-associated virus-based vectors for central nervous system delivery of single-domain immunoglobins/antibodies (VHHs) to inhibit BACE1. In addition, insights into anti-tau therapeutics, including passive immunization and active vaccines, offer novel insights into research. These findings hold implications for the redesign of therapies for neurodegenerative disorders and the advancement of clinical understanding.

Keywords
Neurological condition
Single-domain antibodies
BACE1 inhibition
Tau-related therapeutics
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement. 2022;18:700-789. doi: 10.1002/alz.12638

 

  1. Panza F, Lozupone M, Seripa D, Imbimbo BP. Amyloid-β immunotherapy for Alzheimer disease: Is it now a long shot? Ann Neurol. 2019;85(2):303-315. doi: 10.1002/ana.25415

 

  1. Kabir MT, Uddin MS, Mamun AA, et al. Combination drug therapy for the management of Alzheimer’s disease. Int J Mol Sci. 2020;21:3272. doi: 10.3390/ijms21093272

 

  1. Wolfe MS. Probing mechanisms and therapeutic potential of γ-Secretase in Alzheimer’s disease. Molecules. 2021;26(2):388. doi: 10.3390/molecules26020388

 

  1. Sagnou M, Mavroidi B, Kaminari A, Boukos N, Pelecanou M. Novel isatin thiosemicarbazone derivatives as potent inhibitors of β-Amyloid peptide aggregation and toxicity. ACS Chem Neurosci. 2020;11(16):2266-2276. doi: 10.1021/acschemneuro.0c00364

 

  1. Knopman DS, Amieva H, Petersen RC, et al. Alzheimer disease. Nat Rev Dis Primers. 2021;7:33. doi: 10.1038/s41572-021-00304-9

 

  1. Roda AR, Montoliu-Gaya L, Serra-Mir G, Villegas S. Both amyloid-β peptide and tau protein are affected by an anti-amyloid-β antibody fragment in elderly 3xtg-ad mice. Int J Mol Sci. 2020;21:6630. doi: 10.3390/ijms21010306

 

  1. Busche MA, Hyman BT. The synergy between amyloid-β and tau in Alzheimer’s disease. Nat Neurosci. 2020;23:1183-1193. doi: 10.1038/s41593-020-00742-1

 

  1. 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;12:95. doi: 10.1186/s13195-020-00670-3

 

  1. Singh Gautam A, Pandey SK, Lasure V, Dubey S, Singh RK. Monoclonal antibodies for the management of central nervous system diseases: Clinical success and future strategies. Expert Opin Biol Ther. 2023;23(7):603-618. doi: 10.1080/14712598.2023.2098875

 

  1. Das B, Yan R. A close look at BACE1 inhibitors for Alzheimer’s disease treatment. CNS Drugs. 2019;33(3):251-263. doi: 10.1007/s40263-019-00623-4

 

  1. Lu RM, Hwang YC, Liu IJ, et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci. 2020;27:1. doi: 10.1186/s12929-019-0602-2

 

  1. Pothin E, Lesuisse D, Lafaye P. Brain delivery of single-domain antibodies: A focus on VHH and VNAR. Pharmaceutics. 2020;12:937. doi: 10.3390/pharmaceutics12100937

 

  1. Marino M, Zhou L, Rincon MY, et al. AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer’s disease model. EMBO Mol Med. 2022;14:e09824. doi: 10.15252/emmm.202009824

 

  1. Yadav DB, Maloney JA, Wildsmith KR, et al. Widespread brain distribution and activity following i.c.v. infusion of anti-β-secretase (BACE1) in nonhuman primates. Br J Pharmacol. 2017;174(23):4173-4185. doi: 10.1111/bph.14055

 

  1. Burns S, Selman A, Sehar U, Rawat P, Reddy AP, Reddy PH. Therapeutics of Alzheimer’s disease: Recent developments. Antioxidants (Basel). 2022;11(12):2402. doi: 10.3390/antiox11122402

 

  1. Rawat P, Sehar U, Bisht J, Selman A, Culberson J, Hemachandra Reddy P. Phosphorylated Tau in Alzheimer’s disease and other tauopathies. Int J Mol Sci. 2022;23:12841. doi: 10.3390/ijms232112841

 

  1. Sexton C, Snyder H, Beher D, et al. Current directions in tau research: Highlights from Tau 2020. Alzheimers Dement. 2022;18:988-1007. doi: 10.1002/alz.12452

 

  1. Golde TE. Disease-modifying therapies for Alzheimer’s disease: More questions than answers. Neurotherapeutics. 2022;19:209-227. doi: 10.1007/s13311-022-01201-2

 

  1. Brunello CA, Merezhko M, Uronen RL, Huttunen HJ. Mechanisms of secretion and spreading of pathological tau protein. Cell Mol Life Sci. 2020;77(9):1721-1744. doi: 10.1007/s00018-019-03349-1

 

  1. Panza F, Lozupone M. The challenges of anti-tau therapeutics in Alzheimer’s disease. Nat Rev Neurol. 2022;18:577-578. doi: 10.1038/s41582-022-00702-0

 

  1. Plotkin SS, Cashman NR. Passive immunotherapies targeting Aβ and tau in Alzheimer’s disease. Neurobiol Dis. 2020;144:105010. doi: 10.1016/j.nbd.2020.105010

 

  1. Parrocha CMT, Nowick JS. Current peptide vaccine and immunotherapy approaches against Alzheimer’s disease. Pept Sci (Hoboken). 2023;115:e24289. doi: 10.1002/pep2.24289

 

  1. Galpern WR, Mercken M, Van Kolen K, et al. A single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the anti-phospho-tau antibody JNJ-63733657 in healthy subjects. Alzheimers Dement. 2019;15(7S_Part_5):P252-P253. doi: 10.1016/j.jalz.2019.06.077

 

  1. Guo X, Yan L, Zhang D, Zhao Y. Passive immunotherapy for Alzheimer’s disease. Ageing Res Rev. 2024;94:102192. doi: 10.1016/j.arr.2024.102192

 

  1. Jurcau A, Nunkoo VS. Tau-targeted therapy in Alzheimer’s disease-history and current state. Front Clin Drug Res Dementia. 2021;2:56.

 

  1. Novak P, Zilka N, Zilkova M, et al. AADvac1, an active immunotherapy for Alzheimer’s disease and non-Alzheimer tauopathies: An overview of preclinical and clinical development. J Prev Alzheimers Dis. 2019;6:63-69. doi: 10.14283/jpad.2018.45
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Print ISSN: 2705-0734, Published by AccScience Publishing
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