Recombinant Antibody Fragments for Neurological Disorders: An Update


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:Recombinant antibody fragments are promising alternatives to full-length immunoglobulins, creating big opportunities for the pharmaceutical industry. Nowadays, antibody fragments such as antigen-binding fragments (Fab), single-chain fragment variable (scFv), single-domain antibodies (sdAbs), and bispecific antibodies (bsAbs) are being evaluated as diagnostics or therapeutics in preclinical models and in clinical trials. Immunotherapy approaches, including passive transfer of protective antibodies, have shown therapeutic efficacy in several animal models of Alzheimer´s disease (AD), Parkinson´s disease (PD), frontotemporal dementia (FTD), Huntington´s disease (HD), transmissible spongiform encephalopathies (TSEs) and multiple sclerosis (MS). There are various antibodies approved by the Food and Drug Administration (FDA) for treating multiple sclerosis and two amyloid beta-specific humanized antibodies, Aducanumab and Lecanemab, for AD. Our previous review summarized data on recombinant antibodies evaluated in pre-clinical models for immunotherapy of neurodegenerative diseases. Here, we explore recent studies in this fascinating research field, give an update on new preventive and therapeutic applications of recombinant antibody fragments for neurological disorders and discuss the potential of antibody fragments for developing novel approaches for crossing the blood-brain barrier (BBB) and targeting cells and molecules of interest in the brain.

Sobre autores

Karen Manoutcharian

Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), CDMX

Email: info@benthamscience.net

Goar Gevorkian

Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), CDMX

Autor responsável pela correspondência
Email: info@benthamscience.net

Bibliografia

  1. Bird, R.; Walker, B.W. Single chain antibody variable regions. Trends Biotechnol., 1991, 9(1), 132-137. doi: 10.1016/0167-7799(91)90044-I PMID: 1367550
  2. Morrison, S.L. In vitro antibodies: Strategies for production and application. Annu. Rev. Immunol., 1992, 10(1), 239-265. doi: 10.1146/annurev.iy.10.040192.001323 PMID: 1590987
  3. Plückthun, A.; Pack, P. New protein engineering approaches to multivalent and bispecific antibody fragments. Immunotechnology, 1997, 3(2), 83-105. doi: 10.1016/S1380-2933(97)00067-5 PMID: 9237094
  4. Ma, H.; O’Kennedy, R. Recombinant antibody fragment production. Methods, 2017, 116, 23-33. doi: 10.1016/j.ymeth.2016.11.008 PMID: 27871972
  5. Manoutcharian, K.; Perez-Garmendia, R.; Gevorkian, G. Recombinant antibody fragments for neurodegenerative diseases. Curr. Neuropharmacol., 2017, 15(5), 779-788. doi: 10.2174/1570159X01666160930121647 PMID: 27697033
  6. Pietersz, G.A.; Wang, X.; Yap, M.L.; Lim, B.; Peter, K. Therapeutic targeting in nanomedicine: The future lies in recombinant antibodies. Nanomedicine, 2017, 12(15), 1873-1889. doi: 10.2217/nnm-2017-0043 PMID: 28703636
  7. Bélanger, K.; Iqbal, U.; Tanha, J.; MacKenzie, R.; Moreno, M.; Stanimirovic, D. Single-domain antibodies as therapeutic and imaging agents for the treatment of CNS diseases. Antibodies, 2019, 8(2), 27. doi: 10.3390/antib8020027 PMID: 31544833
  8. Bates, A.; Power, C.A. David vs. Goliath: The structure, function, and clinical prospects of antibody fragments. Antibodies, 2019, 8(2), 28. doi: 10.3390/antib8020028 PMID: 31544834
  9. Salvador, J.P.; Vilaplana, L.; Marco, M.P. Nanobody: Outstanding features for diagnostic and therapeutic applications. Anal. Bioanal. Chem., 2019, 411(9), 1703-1713. doi: 10.1007/s00216-019-01633-4 PMID: 30734854
  10. Pothin, E.; Lesuisse, D.; Lafaye, P. Brain delivery of single-domain antibodies: A focus on VHH and VNAR. Pharmaceutics, 2020, 12(10), 937. doi: 10.3390/pharmaceutics12100937 PMID: 33007904
  11. Gao, Y.; Zhu, J.; Lu, H. Single domain antibody-based vectors in the delivery of biologics across the blood–brain barrier: A review. Drug Deliv. Transl. Res., 2021, 11(5), 1818-1828. doi: 10.1007/s13346-020-00873-7 PMID: 33155179
  12. Roth, K.D.R.; Wenzel, E.V.; Ruschig, M.; Steinke, S.; Langreder, N.; Heine, P.A.; Schneider, K.T.; Ballmann, R.; Fühner, V.; Kuhn, P.; Schirrmann, T.; Frenzel, A.; Dübel, S.; Schubert, M.; Moreira, G.M.S.G.; Bertoglio, F.; Russo, G.; Hust, M. Developing recombinant antibodies by phage display against infectious diseases and toxins for diagnostics and therapy. Front. Cell. Infect. Microbiol., 2021, 11, 697876. doi: 10.3389/fcimb.2021.697876 PMID: 34307196
  13. Ruiz-López, E.; Schuhmacher, A.J. Transportation of single-domain antibodies through the blood–brain barrier. Biomolecules, 2021, 11(8), 1131. doi: 10.3390/biom11081131 PMID: 34439797
  14. Naidoo, D.B.; Chuturgoon, A.A. The potential of nanobodies for COVID-19 diagnostics and therapeutics. Mol. Diagn. Ther., 2023, 27(2), 193-226. doi: 10.1007/s40291-022-00634-x PMID: 36656511
  15. Fuller, J.P.; Stavenhagen, J.B.; Teeling, J.L. New roles for Fc receptors in neurodegeneration-the impact on Immunotherapy for Alzheimer’s Disease. Front. Neurosci., 2014, 8, 235. doi: 10.3389/fnins.2014.00235 PMID: 25191216
  16. Sun, X.; Yu, X.; Zhu, J.; Li, L.; Zhang, L.; Huang, Y.; Liu, D.; Ji, M.; Sun, X.; Zhang, L.; Zhou, W.; Zhang, D.; Jiao, J.; Liu, R. Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer’s disease-like mouse model. Signal Transduct. Target. Ther., 2023, 8(1), 30. doi: 10.1038/s41392-022-01273-8 PMID: 36693826
  17. Huang, L.; Su, X.; Federoff, H. Single-chain fragment variable passive immunotherapies for neurodegenerative diseases. Int. J. Mol. Sci., 2013, 14(9), 19109-19127. doi: 10.3390/ijms140919109 PMID: 24048248
  18. Lulu, S.; Waubant, E. Humoral-targeted immunotherapies in multiple sclerosis. Neurotherapeutics, 2013, 10(1), 34-43. doi: 10.1007/s13311-012-0164-3 PMID: 23208729
  19. Cardinale, A.; Merlo, D.; Giunchedi, P.; Biocca, S. Therapeutic application of intrabodies against age-related neurodegenerative disorders. Curr. Pharm. Des., 2014, 20(38), 6028-6036. doi: 10.2174/1381612820666140314121444 PMID: 24641233
  20. Wootla, B.; Watzlawik, J.O.; Stavropoulos, N.; Wittenberg, N.J.; Dasari, H.; Abdelrahim, M.A.; Henley, J.R.; Oh, S.H.; Warrington, A.E.; Rodriguez, M. Recent advances in monoclonal antibody therapies for multiple sclerosis. Expert Opin. Biol. Ther., 2016, 16(6), 827-839. doi: 10.1517/14712598.2016.1158809 PMID: 26914737
  21. Frontzek, K.; Aguzzi, A. Recent developments in antibody therapeutics against prion disease. Emerg. Top. Life Sci., 2020, 4(2), 169-173. doi: 10.1042/ETLS20200002 PMID: 32633322
  22. Jamwal, S.; Elsworth, J.D.; Rahi, V.; Kumar, P. Gene therapy and immunotherapy as promising strategies to combat Huntington’s disease-associated neurodegeneration: emphasis on recent updates and future perspectives. Expert Rev. Neurother., 2020, 20(11), 1123-1141. doi: 10.1080/14737175.2020.1801424 PMID: 32720531
  23. Panza, F.; Lozupone, M.; Seripa, D.; Daniele, A.; Watling, M.; Giannelli, G.; Imbimbo, B.P. Development of disease-modifying drugs for frontotemporal dementia spectrum disorders. Nat. Rev. Neurol., 2020, 16(4), 213-228. doi: 10.1038/s41582-020-0330-x PMID: 32203398
  24. Haddad, H.W.; Malone, G.W.; Comardelle, N.J.; Degueure, A.E.; Poliwoda, S.; Kaye, R.J.; Murnane, K.S.; Kaye, A.M.; Kaye, A.D. Aduhelm, a novel anti-amyloid monoclonal antibody, for the treatment of Alzheimer’s Disease: A comprehensive review. Health Psychol. Res., 2022, 10(2), 37023. doi: 10.52965/001c.37023 PMID: 35910244
  25. Menon, S.; Armstrong, S.; Hamzeh, A.; Visanji, N.P.; Sardi, S.P.; Tandon, A. Alpha-synuclein targeting therapeutics for Parkinson’s Disease and related synucleinopathies. Front. Neurol., 2022, 13, 852003. doi: 10.3389/fneur.2022.852003 PMID: 35614915
  26. Bateman, R.J.; Cummings, J.; Schobel, S.; Salloway, S.; Vellas, B.; Boada, M.; Black, S.E.; Blennow, K.; Fontoura, P.; Klein, G.; Assunção, S.S.; Smith, J.; Doody, R.S. Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer’s disease. Alzheimers Res. Ther., 2022, 14(1), 178. doi: 10.1186/s13195-022-01110-8 PMID: 36447240
  27. De Genst, E.; Messer, A.; Dobson, C.M. Antibodies and protein misfolding: From structural research tools to therapeutic strategies. Biochim. Biophys. Acta. Proteins Proteomics, 2014, 1844(11), 1907-1919. doi: 10.1016/j.bbapap.2014.08.016 PMID: 25194824
  28. Valera, E.; Spencer, B.; Masliah, E. Immunotherapeutic approaches targeting amyloid-β, α-synuclein, and tau for the treatment of neurodegenerative disorders. Neurotherapeutics, 2016, 13(1), 179-189. doi: 10.1007/s13311-015-0397-z PMID: 26494242
  29. Chia, K.Y.; Ng, K.Y.; Koh, R.Y.; Chye, S.M. Single-chain Fv antibodies for targeting neurodegenerative diseases. CNS Neurol. Disord. Drug Targets, 2018, 17(9), 671-679. doi: 10.2174/1871527317666180315161626 PMID: 29546836
  30. Messer, A.; Butler, D.C. Optimizing intracellular antibodies (intrabodies/nanobodies) to treat neurodegenerative disorders. Neurobiol. Dis., 2020, 134, 104619. doi: 10.1016/j.nbd.2019.104619 PMID: 31669671
  31. Benn, J.A.; Mukadam, A.S.; McEwan, W.A. Targeted protein degradation using intracellular antibodies and its application to neurodegenerative disease. Semin. Cell Dev. Biol., 2022, 126, 138-149. doi: 10.1016/j.semcdb.2021.09.012 PMID: 34654628
  32. Iqbal, K.; Grundke-Iqbal, I. Alzheimer’s disease, a multifactorial disorder seeking multitherapies. Alzheimers Dement., 2010, 6(5), 420-424. doi: 10.1016/j.jalz.2010.04.006 PMID: 20813343
  33. Gong, C.X.; Liu, F.; Iqbal, K. Multifactorial hypothesis and multi-targets for Alzheimer’s Disease. J. Alzheimers Dis., 2018, 64(s1), S107-S117. doi: 10.3233/JAD-179921 PMID: 29562523
  34. Boyd, R.J.; Avramopoulos, D.; Jantzie, L.L.; McCallion, A.S. Neuroinflammation represents a common theme amongst genetic and environmental risk factors for Alzheimer and Parkinson diseases. J. Neuroinflammation, 2022, 19(1), 223. doi: 10.1186/s12974-022-02584-x PMID: 36076238
  35. Penke, B.; Szűcs, M.; Bogár, F. New pathways identify novel drug targets for the prevention and treatment of Alzheimer’s Disease. Int. J. Mol. Sci., 2023, 24(6), 5383. doi: 10.3390/ijms24065383 PMID: 36982456
  36. Selkoe, D.J. Altered structural proteins in plaques and tangles: What do they tell us about the biology of Alzheimer’s disease? Neurobiol. Aging, 1986, 7(6), 425-432. doi: 10.1016/0197-4580(86)90055-2 PMID: 3104810
  37. LaFerla, F.M.; Green, K.N.; Oddo, S. Intracellular amyloid-β in Alzheimer’s disease. Nat. Rev. Neurosci., 2007, 8(7), 499-509. doi: 10.1038/nrn2168 PMID: 17551515
  38. Montoliu-Gaya, L.; Murciano-Calles, J.; Martinez, J.C.; Villegas, S. Towards the improvement in stability of an anti-Aβ single-chain variable fragment, scFv-h3D6, as a way to enhance its therapeutic potential. Amyloid, 2017, 24(3), 167-175. doi: 10.1080/13506129.2017.1348347 PMID: 28699800
  39. Montoliu-Gaya, L.; Mulder, S.D.; Herrebout, M.A.C.; Baayen, J.C.; Villegas, S.; Veerhuis, R. Aβ-oligomer uptake and the resulting inflammatory response in adult human astrocytes are precluded by an anti-Aβ single chain variable fragment in combination with an apoE mimetic peptide. Mol. Cell. Neurosci., 2018, 89, 49-59. doi: 10.1016/j.mcn.2018.03.015 PMID: 29625180
  40. Söllvander, S.; Nikitidou, E.; Brolin, R.; Söderberg, L.; Sehlin, D.; Lannfelt, L.; Erlandsson, A. Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons. Mol. Neurodegener., 2016, 11(1), 38. doi: 10.1186/s13024-016-0098-z PMID: 27176225
  41. Montoliu-Gaya, L.; Esquerda-Canals, G.; Bronsoms, S.; Villegas, S. Production of an anti-Aβ antibody fragment in Pichia pastoris and in vitro and in vivo validation of its therapeutic effect. PLoS One, 2017, 12(8), e0181480. doi: 10.1371/journal.pone.0181480 PMID: 28771492
  42. Esquerda-Canals, G.; Martí-Clúa, J.; Villegas, S. Pharmacokinetic parameters and mechanism of action of an efficient anti-Aβ single chain antibody fragment. PLoS One, 2019, 14(5), e0217793. doi: 10.1371/journal.pone.0217793 PMID: 31150495
  43. Esquerda-Canals, G.; Roda, A.R.; Martí-Clúa, J.; Montoliu-Gaya, L.; Rivera-Hernández, G.; Villegas, S. Treatment with scFv-h3D6 prevented neuronal loss and improved spatial memory in young 3xTg-AD mice by reducing the intracellular amyloid-β burden. J. Alzheimers Dis., 2019, 70(4), 1069-1091. doi: 10.3233/JAD-190484 PMID: 31306135
  44. Güell-Bosch, J.; Lope-Piedrafita, S.; Esquerda-Canals, G.; Montoliu-Gaya, L.; Villegas, S. Progression of Alzheimer’s disease and effect of scFv-h3D6 immunotherapy in the 3xTg-AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy. NMR Biomed., 2020, 33(5), e4263. doi: 10.1002/nbm.4263 PMID: 32067292
  45. Roda, A.R.; 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(18), 6630. doi: 10.3390/ijms21186630 PMID: 32927795
  46. Williams, S.M.; Schulz, P.; Rosenberry, T.L.; Caselli, R.J.; Sierks, M.R. Blood-based oligomeric and other protein variant biomarkers to facilitate pre-symptomatic diagnosis and staging of Alzheimer’s disease. J. Alzheimers Dis., 2017, 58(1), 23-35. doi: 10.3233/JAD-161116 PMID: 28372328
  47. Cho, H.J.; Schulz, P.; Venkataraman, L.; Caselli, R.J.; Sierks, M.R. Sex-specific multiparameter blood test for the early diagnosis of Alzheimer’s Disease. Int. J. Mol. Sci., 2022, 23(24), 15670. doi: 10.3390/ijms232415670 PMID: 36555310
  48. Habiba, U.; Descallar, J.; Kreilaus, F.; Adhikari, U.K.; Kumar, S.; Morley, J.W.; Bui, B.V.; Koronyo-Hamaoui, M.; Tayebi, M. Detection of retinal and blood Aβ oligomers with nanobodies. Alzheimers Dement., 2021, 13(1), e12193. doi: 10.1002/dad2.12193 PMID: 33977118
  49. Li, T.; Vandesquille, M.; Koukouli, F.; Dudeffant, C.; Youssef, I.; Lenormand, P.; Ganneau, C.; Maskos, U.; Czech, C.; Grueninger, F.; Duyckaerts, C.; Dhenain, M.; Bay, S.; Delatour, B.; Lafaye, P. Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets. J. Control. Release, 2016, 243, 1-10. doi: 10.1016/j.jconrel.2016.09.019 PMID: 27671875
  50. Vandesquille, M.; Li, T.; Po, C.; Ganneau, C.; Lenormand, P.; Dudeffant, C.; Czech, C.; Grueninger, F.; Duyckaerts, C.; Delatour, B.; Dhenain, M.; Lafaye, P.; Bay, S. Chemically-defined camelid antibody bioconjugate for the magnetic resonance imaging of Alzheimer’s disease. MAbs, 2017, 9(6), 1016-1027. doi: 10.1080/19420862.2017.1342914 PMID: 28657418
  51. Sebollela, A.; Cline, E.N.; Popova, I.; Luo, K.; Sun, X.; Ahn, J.; Barcelos, M.A.; Bezerra, V.N.; Lyra e Silva, N.M.; Patel, J.; Pinheiro, N.R.; Qin, L.A.; Kamel, J.M.; Weng, A.; DiNunno, N.; Bebenek, A.M.; Velasco, P.T.; Viola, K.L.; Lacor, P.N.; Ferreira, S.T.; Klein, W.L. A human scFv antibody that targets and neutralizes high molecular weight pathogenic amyloid‐β oligomers. J. Neurochem., 2017, 142(6), 934-947. doi: 10.1111/jnc.14118 PMID: 28670737
  52. Cline, E.N.; Bicca, M.A.; Viola, K.L.; Klein, W.L. The amyloid-β oligomer hypothesis: Beginning of the third decade. J. Alzheimers Dis., 2018, 64(S1), S567-S610. doi: 10.3233/JAD-179941 PMID: 29843241
  53. Selles, M.C.; Fortuna, J.T.S.; Cercato, M.C.; Santos, L.E.; Domett, L.; Bitencourt, A.L.B.; Carraro, M.F.; Souza, A.S.; Janickova, H.; Azevedo, C.V.; Campos, H.C.; de Souza, J.M.; Alves-Leon, S.; Prado, V.F.; Prado, M.A.M.; Epstein, A.L.; Salvetti, A.; Longo, B.M.; Arancio, O.; Klein, W.L.; Sebollela, A.; De Felice, F.G.; Jerusalinsky, D.A.; Ferreira, S.T. AAV-mediated neuronal expression of an scFv antibody selective for Aβ oligomers protects synapses and rescues memory in Alzheimer models. Mol. Ther., 2023, 31(2), 409-419. doi: 10.1016/j.ymthe.2022.11.002 PMID: 36369741
  54. Hu, M.; Zhang, J.; Yang, J.; Cao, Y.; Qi, J. A novel scFv Anti-Aβ antibody reduces pathological impairments in APP/PS1 transgenic mice via modulation of inflammatory cytokines and aβ-related enzymes. J. Mol. Neurosci., 2018, 66(1), 1-9. doi: 10.1007/s12031-018-1139-6 PMID: 30062438
  55. Vitale, F.; Giliberto, L.; Ruiz, S.; Steslow, K.; Marambaud, P.; d’Abramo, C. Anti-tau conformational scFv MC1 antibody efficiently reduces pathological tau species in adult JNPL3 mice. Acta Neuropathol. Commun., 2018, 6(1), 82. doi: 10.1186/s40478-018-0585-2 PMID: 30134961
  56. Vitale, F.; Ortolan, J.; Volpe, B.T.; Marambaud, P.; Giliberto, L.; d’Abramo, C. Intramuscular injection of vectorized-scFvMC1 reduces pathological tau in two different tau transgenic models. Acta Neuropathol. Commun., 2020, 8(1), 126. doi: 10.1186/s40478-020-01003-7 PMID: 32762731
  57. Zhang, Y.; Qian, L.; Kuang, Y.; Liu, J.; Wang, D.; Xie, W.; Zhang, L.; Fu, L. An adeno-associated virus-mediated immunotherapy for Alzheimer’s disease. Mol. Immunol., 2022, 144, 26-34. doi: 10.1016/j.molimm.2022.02.006 PMID: 35172225
  58. Danis, C.; Dupré, E.; Zejneli, O.; Caillierez, R.; Arrial, A.; Bégard, S.; Mortelecque, J.; Eddarkaoui, S.; Loyens, A.; Cantrelle, F.X.; Hanoulle, X.; Rain, J.C.; Colin, M.; Buée, L.; Landrieu, I. Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment. Mol. Ther., 2022, 30(4), 1484-1499. doi: 10.1016/j.ymthe.2022.01.009 PMID: 35007758
  59. Guo, T.; Noble, W.; Hanger, D.P. Roles of tau protein in health and disease. Acta Neuropathol., 2017, 133(5), 665-704. doi: 10.1007/s00401-017-1707-9 PMID: 28386764
  60. Spencer, B.; Brüschweiler, S.; Sealey-Cardona, M.; Rockenstein, E.; Adame, A.; Florio, J.; Mante, M.; Trinh, I.; Rissman, R.A.; Konrat, R.; Masliah, E. Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders. Acta Neuropathol., 2018, 136(1), 69-87. doi: 10.1007/s00401-018-1869-0 PMID: 29934874
  61. Panza, F.; Lozupone, M.; Solfrizzi, V.; Sardone, R.; Piccininni, C.; Dibello, V.; Stallone, R.; Giannelli, G.; Bellomo, A.; Greco, A.; Daniele, A.; Seripa, D.; Logroscino, G.; Imbimbo, B.P. BACE inhibitors in clinical development for the treatment of Alzheimer’s disease. Expert Rev. Neurother., 2018, 18(11), 847-857. doi: 10.1080/14737175.2018.1531706 PMID: 30277096
  62. Marino, M.; Zhou, L.; Rincon, M.Y.; Callaerts-Vegh, Z.; Verhaert, J.; Wahis, J.; Creemers, E.; Yshii, L.; Wierda, K.; Saito, T.; Marneffe, C.; Voytyuk, I.; Wouters, Y.; Dewilde, M.; Duqué, S.I.; Vincke, C.; Levites, Y.; Golde, T.E.; Saido, T.C.; Muyldermans, S.; Liston, A.; De Strooper, B.; Holt, M.G. AAV‐mediated delivery of an anti‐BACE1 VHH alleviates pathology in an Alzheimer’s disease model. EMBO Mol. Med., 2022, 14(4), e09824. doi: 10.15252/emmm.201809824 PMID: 35352880
  63. Fahrenholz, F. Alpha-secretase as a therapeutic target. Curr. Alzheimer Res., 2007, 4(4), 412-417. doi: 10.2174/156720507781788837 PMID: 17908044
  64. Lichtenthaler, S.F.; Tschirner, S.K.; Steiner, H. Secretases in Alzheimer’s disease: Novel insights into proteolysis of APP and TREM2. Curr. Opin. Neurobiol., 2022, 72, 101-110. doi: 10.1016/j.conb.2021.09.003 PMID: 34689040
  65. He, P.; Xin, W.; Schulz, P.; Sierks, M.R. Bispecific antibody fragment targeting app and inducing α-site cleavage restores neuronal health in an alzheimer’s mouse model. Mol. Neurobiol., 2019, 56(11), 7420-7432. doi: 10.1007/s12035-019-1597-z PMID: 31041656
  66. Zhao, L.; Meng, F.; Li, Y.; Liu, S.; Xu, M.; Chu, F.; Li, C.; Yang, X.; Luo, L. Multivalent nanobody conjugate with rigid, reactive oxygen species scavenging scaffold for multi‐target therapy of Alzheimer’s Disease. Adv. Mater., 2023, 35(17), 2210879. doi: 10.1002/adma.202210879 PMID: 36786375
  67. Saleh, M.; Markovic, M.; Olson, K.E.; Gendelman, H.E.; Mosley, R.L. Therapeutic strategies for immune transformation in parkinson’s disease. J. Parkinsons Dis., 2022, 12(s1), S201-S222. doi: 10.3233/JPD-223278 PMID: 35871362
  68. Massey, A.; Boag, M.; Magnier, A.; Bispo, D.; Khoo, T.; Pountney, D. Glymphatic system dysfunction and sleep disturbance may contribute to the pathogenesis and progression of Parkinson’s Disease. Int. J. Mol. Sci., 2022, 23(21), 12928. doi: 10.3390/ijms232112928 PMID: 36361716
  69. Dong-Chen, X.; Yong, C.; Yang, X.; Chen-Yu, S.; Li-Hua, P. Signaling pathways in Parkinson’s disease: Molecular mechanisms and therapeutic interventions. Signal Transduct. Target. Ther., 2023, 8(1), 73. doi: 10.1038/s41392-023-01353-3 PMID: 36810524
  70. Forloni, G. Alpha synuclein: Neurodegeneration and inflammation. Int. J. Mol. Sci., 2023, 24(6), 5914. doi: 10.3390/ijms24065914 PMID: 36982988
  71. Castonguay, A-M.; Gravel, C.; Lévesque, M. Treating Parkinson’s Disease with antibodies: Previous studies and future directions. J. Parkinsons Dis., 2021, 11(1), 71-92. doi: 10.3233/JPD-202221
  72. Knecht, L.; Folke, J.; Dodel, R.; Ross, J.A.; Albus, A. Alpha-synuclein immunization strategies for synucleinopathies in clinical studies: A biological perspective. Neurotherapeutics, 2022, 19(5), 1489-1502. doi: 10.1007/s13311-022-01288-7 PMID: 36083395
  73. Gupta, V.; Salim, S.; Hmila, I.; Vaikath, N.N.; Sudhakaran, I.P.; Ghanem, S.S.; Majbour, N.K.; Abdulla, S.A.; Emara, M.M.; Abdesselem, H.B.; Lukacsovich, T.; Erskine, D.; El-Agnaf, O.M.A. Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity. Sci. Rep., 2020, 10(1), 8137. doi: 10.1038/s41598-020-65035-8 PMID: 32424162
  74. Gupta, V.; Sudhakaran, I.P.; Islam, Z.; Vaikath, N.N.; Hmila, I.; Lukacsovich, T.; Kolatkar, P.R.; El-Agnaf, O.M.A. Expression, purification and characterization of α-synuclein fibrillar specific scFv from inclusion bodies. PLoS One, 2020, 15(11), e0241773. doi: 10.1371/journal.pone.0241773 PMID: 33156828
  75. Fassler, M.; Benaim, C.; George, J. A single chain fragment variant binding misfolded alpha-synuclein exhibits neuroprotective and antigen-specific anti-inflammatory properties. Cells, 2022, 11(23), 3822. doi: 10.3390/cells11233822 PMID: 36497081
  76. Hmila, I.; Vaikath, N.N.; Majbour, N.K.; Erskine, D.; Sudhakaran, I.P.; Gupta, V.; Ghanem, S.S.; Islam, Z.; Emara, M.M.; Abdesselem, H.B.; Kolatkar, P.R.; Achappa, D.K.; Vinardell, T.; El-Agnaf, O.M.A. Novel engineered nanobodies specific for N-terminal region of alpha-synuclein recognize Lewy‐body pathology and inhibit in-vitro seeded aggregation and toxicity. FEBS J., 2022, 289(15), 4657-4673. doi: 10.1111/febs.16376 PMID: 35090199
  77. Cookson, M.R. LRRK2 pathways leading to neurodegeneration. Curr. Neurol. Neurosci. Rep., 2015, 15(7), 42. doi: 10.1007/s11910-015-0564-y PMID: 26008812
  78. Gilligan, P. Inhibitors of leucine-rich repeat kinase 2 (LRRK2): Progress and promise for the treatment of Parkinson’s disease. Curr. Top. Med. Chem., 2015, 15(10), 927-938. doi: 10.2174/156802661510150328223655 PMID: 25832719
  79. Mata, I.; Salles, P.; Cornejo-Olivas, M.; Saffie, P.; Ross, O.A.; Reed, X.; Bandres-Ciga, S. LRRK2: Genetic mechanisms vs genetic subtypes. Handb. Clin. Neurol., 2023, 193, 133-154. doi: 10.1016/B978-0-323-85555-6.00018-7 PMID: 36803807
  80. Taymans, J.M.; Greggio, E. LRRK2 kinase inhibition as a therapeutic strategy for Parkinson’s disease, where do we stand? Curr. Neuropharmacol., 2016, 14(3), 214-225. doi: 10.2174/1570159X13666151030102847 PMID: 26517051
  81. Singh, R.K.; Soliman, A.; Guaitoli, G.; Störmer, E.; von Zweydorf, F.; Dal Maso, T.; Oun, A.; Van Rillaer, L.; Schmidt, S.H.; Chatterjee, D.; David, J.A.; Pardon, E.; Schwartz, T.U.; Knapp, S.; Kennedy, E.J.; Steyaert, J.; Herberg, F.W.; Kortholt, A.; Gloeckner, C.J.; Versées, W. Nanobodies as allosteric modulators of Parkinson’s disease–associated LRRK2. Proc. Natl. Acad. Sci., 2022, 119(9), e2112712119. doi: 10.1073/pnas.2112712119 PMID: 35217606
  82. Rüb, U.; Vonsattel, J.P.G.; Heinsen, H.; Korf, H.W. The neuropathology of Huntington’s disease: Classical findings, recent developments and correlation to functional neuroanatomy. Adv. Anat. Embryol. Cell Biol., 2015, 217, 1-146. doi: 10.1007/978-3-319-19285-7 PMID: 26767207
  83. Palaiogeorgou, A.; Papakonstantinou, E.; Golfinopoulou, R.; Sigala, M.; Mitsis, T.; Papageorgiou, L.; Diakou, I.; Pierouli, K.; Dragoumani, K.; Spandidos, D.; Bacopoulou, F.; Chrousos, G.; Eliopoulos, E.; Vlachakis, D. Recent approaches on Huntington’s disease (Review). Biomed. Rep., 2022, 18(1), 5. doi: 10.3892/br.2022.1587 PMID: 36544856
  84. Khoshnan, A.; Ou, S.; Ko, J.; Patterson, P.H. Antibodies and intrabodies against huntingtin: production and screening of monoclonals and single-chain recombinant forms. Methods Mol. Biol., 2013, 1010, 231-251. doi: 10.1007/978-1-62703-411-1_15 PMID: 23754229
  85. Denis, H.L.; David, L.S.; Cicchetti, F. Antibody-based therapies for Huntington’s disease: Current status and future directions. Neurobiol. Dis., 2019, 132, 104569. doi: 10.1016/j.nbd.2019.104569 PMID: 31398458
  86. Amaro, I.A.; Henderson, L.A. An intrabody drug (rAAV6-INT41) reduces the binding of N-terminal huntingtin fragment(s) to DNA to basal levels in PC12 cells and delays cognitive loss in the R6/2 animal model. J. Neurodegener. Dis., 2016, 2016, 1-10. doi: 10.1155/2016/7120753 PMID: 27595037
  87. Perche, F.; Uchida, S.; Akiba, H.; Lin, C.Y.; Ikegami, M.; Dirisala, A.; Nakashima, T.; Itaka, K.; Tsumoto, K.; Kataoka, K. Improved brain expression of anti-amyloid β scFv by complexation of mRNA including a secretion sequence with PEG-based block catiomer. Curr. Alzheimer Res., 2017, 14(3), 295-302. doi: 10.2174/1567205013666161108110031 PMID: 27829339
  88. Xie, J.; Gonzalez-Carter, D.; Tockary, T.A.; Nakamura, N.; Xue, Y.; Nakakido, M.; Akiba, H.; Dirisala, A.; Liu, X.; Toh, K.; Yang, T.; Wang, Z.; Fukushima, S.; Li, J.; Quader, S.; Tsumoto, K.; Yokota, T.; Anraku, Y.; Kataoka, K. Dual-sensitive nanomicelles enhancing systemic delivery of therapeutically active antibodies specifically into the brain. ACS Nano, 2020, 14(6), 6729-6742. doi: 10.1021/acsnano.9b09991 PMID: 32431145
  89. Tsitokana, M.E.; Lafon, P.A.; Prézeau, L.; Pin, J.P.; Rondard, P. Targeting the brain with single-domain antibodies: Greater potential than stated so far? Int. J. Mol. Sci., 2023, 24(3), 2632. doi: 10.3390/ijms24032632 PMID: 36768953
  90. Hultqvist, G.; Syvänen, S.; Fang, X.T.; Lannfelt, L.; Sehlin, D. Bivalent brain shuttle increases antibody uptake by monovalent binding to the transferrin receptor. Theranostics, 2017, 7(2), 308-318. doi: 10.7150/thno.17155 PMID: 28042336
  91. Meier, S.R.; Syvänen, S.; Hultqvist, G.; Fang, X.T.; Roshanbin, S.; Lannfelt, L.; Neumann, U.; Sehlin, D. Antibody-based in vivo PET imaging detects amyloid-β reduction in alzheimer transgenic mice after BACE-1 inhibition. J. Nucl. Med., 2018, 59(12), 1885-1891. doi: 10.2967/jnumed.118.213140 PMID: 29853653
  92. Fang, X.T.; Hultqvist, G.; Meier, S.R.; Antoni, G.; Sehlin, D.; Syvänen, S. High detection sensitivity with antibody-based PET radioligand for amyloid beta in brain. Neuroimage, 2019, 184, 881-888. doi: 10.1016/j.neuroimage.2018.10.011 PMID: 30300753
  93. Stocki, P.; Szary, J.; Rasmussen, C.L.M.; Demydchuk, M.; Northall, L.; Logan, D.B.; Gauhar, A.; Thei, L.; Moos, T.; Walsh, F.S.; Rutkowski, J.L. Blood‐brain barrier transport using a high affinity, brain‐selective VNAR antibody targeting transferrin receptor 1. FASEB J., 2021, 35(2), e21172. doi: 10.1096/fj.202001787R PMID: 33241587
  94. Syvänen, S.; Fang, X.T.; Hultqvist, G.; Meier, S.R.; Lannfelt, L.; Sehlin, D. A bispecific Tribody PET radioligand for visualization of amyloid-beta protofibrils – a new concept for neuroimaging. Neuroimage, 2017, 148, 55-63. doi: 10.1016/j.neuroimage.2017.01.004 PMID: 28069541
  95. Rofo, F.; Meier, S.R.; Metzendorf, N.G.; Morrison, J.I.; Petrovic, A.; Syvänen, S.; Sehlin, D.; Hultqvist, G. A brain-targeting bispecific-multivalent antibody clears soluble amyloid-beta aggregates in alzheimer’s disease mice. Neurotherapeutics, 2022, 19(5), 1588-1602. doi: 10.1007/s13311-022-01283-y PMID: 35939261
  96. Sehlin, D.; Stocki, P.; Gustavsson, T.; Hultqvist, G.; Walsh, F.S.; Rutkowski, J.L.; Syvänen, S. Brain delivery of biologics using a cross-species reactive transferrin receptor 1 VNAR shuttle. FASEB J., 2020, 34(10), 13272-13283. doi: 10.1096/fj.202000610RR PMID: 32779267
  97. Clarke, E.; Stocki, P.; Sinclair, E.H.; Gauhar, A.; Fletcher, E.J.R.; Krawczun-Rygmaczewska, A.; Duty, S.; Walsh, F.S.; Doherty, P.; Rutkowski, J.L. A single domain shark antibody targeting the transferrin receptor 1 delivers a TrkB agonist antibody to the brain and provides full neuroprotection in a mouse model of Parkinson’s Disease. Pharmaceutics, 2022, 14(7), 1335. doi: 10.3390/pharmaceutics14071335 PMID: 35890231
  98. Wouters, Y.; Jaspers, T.; Rué, L.; Serneels, L.; De Strooper, B.; Dewilde, M. VHHs as tools for therapeutic protein delivery to the central nervous system. Fluids Barriers CNS, 2022, 19(1), 79. doi: 10.1186/s12987-022-00374-4 PMID: 36192747
  99. Alata, W.; Yogi, A.; Brunette, E.; Delaney, C.E.; Faassen, H.; Hussack, G.; Iqbal, U.; Kemmerich, K.; Haqqani, A.S.; Moreno, M.J.; Stanimirovic, D.B. Targeting insulin‐like growth factor‐1 receptor (IGF1R) for brain delivery of biologics. FASEB J., 2022, 36(3), e22208. doi: 10.1096/fj.202101644R PMID: 35192204
  100. Yogi, A.; Hussack, G.; van Faassen, H.; Haqqani, A.S.; Delaney, C.E.; Brunette, E.; Sandhu, J.K.; Hewitt, M.; Sulea, T.; Kemmerich, K.; Stanimirovic, D.B. Brain delivery of IGF1R5, a single-domain antibody targeting insulin-like growth factor-1 receptor. Pharmaceutics, 2022, 14(7), 1452. doi: 10.3390/pharmaceutics14071452 PMID: 35890347
  101. Aguiar, S.I.; Días, J.N.R.; André, A.S.; Silva, M.L.; Martins, D.; Carrapiço, B.; Castanho, M.; Carriço, J.; Cavaco, M.; Gaspar, M.M.; Nobre, R.J.; Pereira de Almeida, L.; Oliveira, S.; Gano, L.; Correia, J.D.G.; Barbas, C., III; Gonçalves, J.; Neves, V.; Aires-da-Silva, F. Highly specific blood-brain barrier transmigrating single-domain antibodies selected by an in vivo phage display screening. Pharmaceutics, 2021, 13(10), 1598. doi: 10.3390/pharmaceutics13101598 PMID: 34683891
  102. Vangijzegem, T.; Lecomte, V.; Ternad, I.; Van Leuven, L.; Muller, R.N.; Stanicki, D.; Laurent, S. Superparamagnetic iron oxide nanoparticles (SPION): From fundamentals to state-of-the-art innovative applications for cancer therapy. Pharmaceutics, 2023, 15(1), 236. doi: 10.3390/pharmaceutics15010236 PMID: 36678868
  103. Liu, X.; Lu, S.; Liu, D.; Zhang, L.; Zhang, L.; Yu, X.; Liu, R. ScFv-conjugated superparamagnetic iron oxide nanoparticles for MRI-based diagnosis in transgenic mouse models of Parkinson’s and Huntington’s diseases. Brain Res., 2019, 1707, 141-153. doi: 10.1016/j.brainres.2018.11.034 PMID: 30481502
  104. Liu, X.G.; Zhang, L.; Lu, S.; Liu, D.Q.; Zhang, L.X.; Yu, X.L.; Liu, R.T. Multifunctional superparamagnetic iron oxide nanoparticles conjugated with Aβ oligomer-specific scFv antibody and class a scavenger receptor activator show early diagnostic potentials for Alzheimer’s Disease. Int. J. Nanomedicine, 2020, 15, 4919-4932. doi: 10.2147/IJN.S240953 PMID: 32764925
  105. Liu, X.; Zhang, L.; Lu, S.; Liu, D.; Huang, Y.; Zhu, J.; Zhou, W.; Yu, X.; Liu, R. Superparamagnetic iron oxide nanoparticles conjugated with Aβ oligomer-specific scFv antibody and class A scavenger receptor activator show therapeutic potentials for Alzheimer’s disease. J. Nanobiotechnology, 2020, 18(1), 160. doi: 10.1186/s12951-020-00723-1 PMID: 33160377

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