Antibody Approaches To Treat Brain Diseases

Trends in Biotechnology

Volumn 34, Issue 1, 2016, Pages 36-48

  Neves, Vera ^a   Aires da Silva, Frederico ^b   Corte Real, Sofia ^c   Castanho, Miguel A R B ^a  

^a INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

^b FACULDADE DE MEDICINA VETERINÁRIA   (Portugal)

^c Technophage SA   (Portugal)

Author keywords

Bispecific antibodies; Blood brain barrier; Brain drug delivery; Central nervous system disorders; Molecular trojan horses (MTH); Recombinant antibodies

Indexed keywords

BLOOD; NEUROPHYSIOLOGY;

BLOOD-BRAIN BARRIER; BRAIN DRUG DELIVERIES; CENTRAL NERVOUS SYSTEMS; MOLECULAR TROJAN HORSES (MTH); RECOMBINANT ANTIBODY;

ANTIBODIES;

RECOMBINANT ANTIBODY;

ANTIBODY ENGINEERING; BLOOD BRAIN BARRIER; BRAIN DISEASE; DRUG EFFICACY; DRUG MECHANISM; DRUG PENETRATION; DRUG TARGETING; DRUG TRANSPORT; HUMAN; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW;

EID: 84955244848     PISSN: 01677799     EISSN: 18793096     Source Type: Journal    
DOI: 10.1016/j.tibtech.2015.10.005     Document Type: Review

References (76)

1. Miller M. Brain Facts: A Primer on the Brain and Nervous System 2012, Society for Neuroscience.
2. Collins P.Y., et al. Grand challenges in global mental health. Nature 2011, 475:27-30.
3. Honjo K., et al. Alzheimer's disease, cerebrovascular disease, and the beta-amyloid cascade. Can. J. Neurol. Sci. 2012, 39:712-728.
4. Baumgart M., et al. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective. Alzheimers Dement. 2015, 11:718-726.
5. Prince M., et al. Policy Brief for Heads of Government: The Global Impact of Dementia 2013-2050 2013, Alzheimer's Disease International.
6. Thorne R.G., Frey W.H. Delivery of neurotrophic factors to the central nervous system: pharmacokinetic considerations. Clin. Pharmacokinet. 2001, 40:907-946.
7. Nagahara A.H., Tuszynski M.H. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat. Rev. Drug Discov. 2011, 10:209-219.
8. Neuwelt E., et al. Strategies to advance translational research into brain barriers. Lancet Neurol. 2008, 7:84-96.
9. Abbott N.J., et al. Structure and function of the blood-brain barrier. Neurobiol. Dis. 2010, 37:13-25.
10. Neuwelt E.A., et al. Engaging neuroscience to advance translational research in brain barrier biology. Nat. Rev. Neurosci. 2011, 12:169-182.
11. Pardridge W.M. The blood-brain barrier: bottleneck in brain drug development. NeuroRx. 2005, 2:3-14.
12. Wilson E.H., et al. Trafficking of immune cells in the central nervous system. J. Clin. Invest. 2010, 120:1368-1379.
13. Muldoon L.L., et al. Immunologic privilege in the central nervous system and the blood-brain barrier. J. Cereb. Blood Flow Metab. 2013, 33:13-21.
14. Georgieva J.V., et al. Smuggling drugs into the brain: an overview of ligands targeting transcytosis for drug delivery across the blood-brain barrier. Pharmaceutics 2014, 6:557-583.
15. Ballabh P., et al. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol. Dis. 2004, 16:1-13.
16. Huber J.D., et al. Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci. 2001, 24:719-725.
17. Yong V.W. Metalloproteinases: mediators of pathology and regeneration in the CNS. Nat. Rev. Neurosci. 2005, 6:931-944.
18. Daneman R., et al. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 2010, 468:562-566.
19. Coomber B.L., Stewart P.A. Three-dimensional reconstruction of vesicles in endothelium of blood-brain barrier versus highly permeable microvessels. Anat. Rec. 1986, 215:256-261.
20. Brillault J., et al. Intercommunications between brain capillary endothelial cells and glial cells increase the transcellular permeability of the blood-brain barrier during ischaemia. J. Neurochem. 2002, 83:807-817.
21. Pardridge W.M. Blood-brain barrier delivery. Drug Discov. Today 2007, 12:54-61.
22. Patel M.M., et al. Getting into the brain: approaches to enhance brain drug delivery. CNS Drugs 2009, 23:35-58.
23. Gabathuler R. Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases. Neurobiol. Dis. 2010, 37:48-57.
24. Soni V., et al. Potential approaches for drug delivery to the brain: past, present, and future. Crit. Rev. Ther. Drug Carrier Syst. 2010, 27:187-236.
25. Pardridge W.M., Boado R.J. Reengineering biopharmaceuticals for targeted delivery across the blood-brain barrier. Methods Enzymol. 2012, 503:269-292.
26. Pardridge W.M. Re-engineering biopharmaceuticals for delivery to brain with molecular Trojan horses. Bioconjug. Chem. 2008, 19:1327-1338.
27. Pardridge W.M. Drug and gene targeting to the brain with molecular Trojan horses. Nat. Rev. Drug Discov. 2002, 1:131-139.
28. Pardridge W.M. Molecular Trojan horses for blood-brain barrier drug delivery. Curr. Opin. Pharmacol. 2006, 6:494-500.
29. Aires da Silva F., et al. Recombinant antibodies as therapeutic agents: pathways for modeling new biodrugs. BioDrugs 2008, 22:13.
30. Fishman J.B., et al. Receptor-mediated transcytosis of transferrin across the blood-brain barrier. J. Neurosci. Res. 1987, 18:299-304.
31. Roberts R.L., et al. Receptor-mediated endocytosis of transferrin at the blood-brain barrier. J Cell Sci. 1993, 104:521-532.
32. Lee H.J., et al. Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse. J. Pharmacol. Exp. Ther. 2000, 292:1048-1052.
33. Jones A.R., Shusta E.V. Blood-brain barrier transport of therapeutics via receptor-mediation. Pharm. Res. 2007, 24:1759-1771.
34. Pardridge W.M. Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody. Expert Opin. Drug Deliv. 2015, 12:207-222.
35. Zhang Y., Pardridge W.M. Blood-brain barrier targeting of BDNF improves motor function in rats with middle cerebral artery occlusion. Brain Res. 2006, 1111:227-229.
36. Kordower J.H., et al. Intravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease. Proc. Natl. Acad. Sci. U.S.A. 1994, 91:9077-9080.
37. Zhou Q.H., et al. Monoclonal antibody-glial-derived neurotrophic factor fusion protein penetrates the blood-brain barrier in the mouse. Drug Metab. Dispos. 2010, 38:566-572.
38. Yu Y.J., et al. Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target. Sci. Transl. Med. 2011, 3:84ra44.
39. Pardridge W.M., et al. Human insulin receptor monoclonal antibody undergoes high affinity binding to human brain capillaries in vitro and rapid transcytosis through the blood-brain barrier in vivo in the primate. Pharm. Res. 1995, 12:807-816.
40. Coloma M.J., et al. Transport across the primate blood-brain barrier of a genetically engineered chimeric monoclonal antibody to the human insulin receptor. Pharm. Res. 2000, 17:266-274.
41. Boado R.J., et al. Humanization of anti-human insulin receptor antibody for drug targeting across the human blood-brain barrier. Biotechnol. Bioeng. 2007, 96:381-391.
42. Ohshima-Hosoyama S., et al. A monoclonal antibody-GDNF fusion protein is not neuroprotective and is associated with proliferative pancreatic lesions in parkinsonian monkeys. PLoS ONE 2012, 7:e39036.
43. Couch J.A., et al. Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier. Sci. Transl. Med. 2013, 5:183ra57.
44. Muruganandam A., et al. Selection of phage-displayed llama single-domain antibodies that transmigrate across human blood-brain barrier endothelium. FASEB J. 2002, 16:240-242.
45. Haqqani A.S., et al. Multiplexed evaluation of serum and CSF pharmacokinetics of brain-targeting single-domain antibodies using a NanoLC-SRM-ILIS method. Mol. Pharm. 2013, 10:1542-1556.
46. Iqbal U., et al. Kinetic analysis of novel mono- and multivalent VHH-fragments and their application for molecular imaging of brain tumours. Br. J. Pharmacol. 2010, 160:1016-1028.
47. Wang X.X., et al. Mining a yeast library for brain endothelial cell-binding antibodies. Nat. Methods 2007, 4:143-145.
48. Kontermann R.E., Brinkmann U. Bispecific antibodies. Drug Discov. Today 2015, 20:838-847.
49. Stanimirovic D., et al. Engineering and pharmacology of blood-brain barrier-permeable bispecific antibodies. Adv. Pharmacol. 2014, 71:301-335.
50. Watts R.J., Dennis M.S. Bispecific antibodies for delivery into the brain. Curr. Opin. Chem. Biol. 2013, 17:393-399.
51. Sumbria R.K., et al. Disaggregation of amyloid plaque in brain of Alzheimer's disease transgenic mice with daily subcutaneous administration of a tetravalent bispecific antibody that targets the transferrin receptor and the Abeta amyloid peptide. Mol. Pharm. 2013, 10:3507-3513.
52. Boado R.J., et al. Fusion antibody for Alzheimer's disease with bidirectional transport across the blood-brain barrier and Abeta fibril disaggregation. Bioconjug. Chem. 2007, 18:447-455.
53. Yu Y.J., et al. Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman primates. Sci. Transl. Med. 2014, 6:261ra154.
54. Niewoehner J., et al. Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle. Neuron 2014, 81:49-60.
55. Farrington G.K., et al. A novel platform for engineering blood-brain barrier-crossing bispecific biologics. FASEB J. 2014, 28:4764-4778.
56. DeMattos R.B., et al. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. U.S.A. 2001, 98:8850-8855.
57. Spencer B., Masliah E. Immunotherapy for Alzheimer's disease: past, present and future. Front. Aging Neurosci. 2014, 6:114.
58. Solomon B., et al. Monoclonal antibodies inhibit in vitro fibrillar aggregation of the Alzheimer beta-amyloid peptide. Proc. Natl. Acad. Sci. U.S.A. 1996, 93:452-455.
59. Hefti F., et al. The case for soluble Abeta oligomers as a drug target in Alzheimer's disease. Trends Pharmacol. Sci. 2013, 34:261-266.
60. Reardon S. Antibody drugs for Alzheimer's show glimmers of promise. Nature 2015, 523:509-510.
61. Salloway S., et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N. Engl. J. Med. 2014, 370:322-333.
62. Doody R.S., et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N. Engl. J. Med. 2014, 370:311-321.
63. Jacobsen H., et al. Combined treatment with a BACE inhibitor and anti-Abeta antibody gantenerumab enhances amyloid reduction in APPLondon mice. J. Neurosci. 2014, 34:11621-11630.
64. Bohrmann B., et al. Gantenerumab: a novel human anti-Abeta antibody demonstrates sustained cerebral amyloid-beta binding and elicits cell-mediated removal of human amyloid-beta. J. Alzheimers Dis. 2012, 28:49-69.
65. Adolfsson O., et al. An effector-reduced anti-beta-amyloid (Abeta) antibody with unique abeta binding properties promotes neuroprotection and glial engulfment of Abeta. J. Neurosci. 2012, 32:9677-9689.
66. Burstein A.H., et al. Safety and pharmacology of ponezumab (PF-04360365) after a single 10-minute intravenous infusion in subjects with mild to moderate Alzheimer disease. Clin. Neuropharmacol. 2013, 36:8-13.
67. Patel K.R. Biogen's aducanumab raises hope that Alzheimer's can be treated at its source. Manag. Care 2015, 24:19.
68. Boado R.J., Pardridge W.M. Comparison of blood-brain barrier transport of glial-derived neurotrophic factor (GDNF) and an IgG-GDNF fusion protein in the rhesus monkey. Drug Metab. Dispos. 2009, 37:2299-2304.
69. Sumbria R.K., et al. Brain protection from stroke with intravenous TNFalpha decoy receptor-Trojan horse fusion protein. J. Cereb. Blood Flow Metab. 2012, 32:1933-1938.
70. Sumbria R.K., et al. Pharmacokinetics and brain uptake of an IgG-TNF decoy receptor fusion protein following intravenous, intraperitoneal, and subcutaneous administration in mice. Mol. Pharm. 2013, 10:1425-1431.
71. Sumbria R.K., et al. Combination stroke therapy in the mouse with blood-brain barrier penetrating IgG-GDNF and IgG-TNF decoy receptor fusion proteins. Brain Res. 2013, 1507:91-96.
72. Boado R.J., et al. Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein. J. Biotechnol. 2010, 146:84-91.
73. Boado R.J., et al. IgG-single chain Fv fusion protein therapeutic for Alzheimer's disease: expression in CHO cells and pharmacokinetics and brain delivery in the rhesus monkey. Biotechnol. Bioeng. 2010, 105:627-635.
74. Boado R.J., et al. Pharmacokinetics and brain uptake in the rhesus monkey of a fusion protein of arylsulfatase a and a monoclonal antibody against the human insulin receptor. Biotechnol. Bioeng. 2013, 110:1456-1465.
75. Boado R.J., et al. Insulin receptor antibody-sulfamidase fusion protein penetrates the primate blood-brain barrier and reduces glycosoaminoglycans in Sanfilippo type A cells. Mol. Pharm. 2014, 11:2928-2934.
76. Atwal J.K., et al. A therapeutic antibody targeting BACE1 inhibits amyloid-beta production in vivo. Sci. Transl. Med. 2011, 3:84ra43.