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

Molecular Pharmaceutics

Volumn 10, Issue 9, 2013, Pages 3507-3513

  Sumbria, Rachita K ^a   Hui, Eric Ka Wai ^b   Lu, Jeff Zhiqiang ^b   Boado, Ruben J ^a,b   Pardridge, William M ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b ArmaGen Technologies Inc   (United States)

Author keywords

Alzheimer's disease; amyloid; Blood brain barrier; monoclonal antibody; transferrin receptor

Indexed keywords

AMYLOID; AMYLOID BETA PROTEIN; BISPECIFIC ANTIBODY; HYBRID PROTEIN; PRESENILIN; TRANSFERRIN RECEPTOR;

ALZHEIMER DISEASE; AMYLOID PLAQUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY RESPONSE; ANTIBODY TITER; ARTICLE; BRAIN CORTEX; CONFOCAL MICROSCOPY; CONTROLLED STUDY; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; ANTIBODIES, BISPECIFIC; ANTIBODIES, MONOCLONAL; BRAIN; MICE; MICE, TRANSGENIC; PLAQUE, AMYLOID; RECEPTORS, TRANSFERRIN;

EID: 84883591583     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp400348n     Document Type: Article

References (32)

1. Cummings, B. J.; Cotman, C. W. Image analysis of beta-amyloid load in Alzheimer's disease and relation to dementia severity Lancet 1995, 346 (8989) 1524-1528
2. Naslund, J.; Haroutunian, V.; Mohs, R.; Davis, K. L.; Davies, P.; Greengard, P.; Buxbaum, J. D. Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline JAMA, J. Am. Med. Assoc. 2000, 283 (12) 1571-1577
3. Glenner, G. G.; Wong, C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein Biochem. Biophys. Res. Commun. 1984, 120 (3) 885-890
4. Masters, C. L.; Simms, G.; Weinman, N. A.; Multhaup, G.; McDonald, B. L.; Beyreuther, K. Amyloid plaque core protein in Alzheimer disease and Down syndrome Proc. Natl. Acad. Sci. U.S.A. 1985, 82 (12) 4245-4249
5. Solomon, B.; Kippel, R.; Frankel, D.; Hanan-Aharon, E. Disaggregation of Alzheimer β-amyloid by site-directed mAb Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 4109-4112
6. 11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study Lancet Neurol. 2010, 9, 363-372
7. Bohrmann, B.; Baumann, K.; Benz, J.; Gerber, F.; Huber, W.; Knolfach, F.; Messer, J.; Oroszlan, K.; Rachenberger, R.; Richter, W. F.; Rothe, C.; Urban, M.; Bardroff, M.; Winter, M.; Nordstedt, C.; Loetscher, H. Gantenerumab: A novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β J. Alzheimer's Dis. 2012, 28, 49-69
8. Boado, R. J.; Zhang, Y.; Xia, C. F.; Pardridge, W. M. Fusion antibody for Alzheimer's disease with bidirectional transport across the blood-brain barrier and abeta fibril disaggregation Bioconjugate Chem. 2007, 18 (2) 447-455
9. Boado, R. J.; Zhou, Q. H.; Lu, J. Z.; Hui, E. K.; Pardridge, W. M. Pharmacokinetics and brain uptake of a genetically engineered bifunctional fusion antibody targeting the mouse transferrin receptor Mol. Pharmaceutics 2010, 7, 237-244
10. Zhang, Y.; Pardridge, W. M. Mediated efflux of IgG molecules from brain to blood across the blood-brain barrier J. Neuroimmunol. 2001, 114, 168-172
11. Schlachetzki, F.; Zhu, C.; Pardridge, W. M. Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier J. Neurochem. 2002, 81, 203-206
12. Siemers, E. R.; Friedrich, S.; Dean, R. A.; Gonzales, C. R.; Farlow, M. R.; Paul, S. M.; DeMattos, R. B. Safety and changes in plasma and cerebrospinal fluid amyloid β after a single administration of an amyloid β monoclonal antibody in subjects with Alzheimer disease Clin. Neuropharmacol. 2010, 33, 67-73
13. Black, R. S.; Sperling, R. A.; Safirstein, B.; Motter, R. N.; Pallay, A.; Nichols, A.; Grundman, M. A single ascending dose study of bapineuzumab in patients with Alzheimer disease Alzheimer Dis. Assoc. Disord. 2010, 24, 198-203
14. Bard, F.; Cannon, C.; Barbour, R.; Burke, R. L.; Games, D.; Grajeda, H.; Guido, T.; Hu, K.; Huang, J.; Johnson-Wood, K.; Khan, K.; Kholodenko, D.; Lee, M.; Lieberburg, I.; Motter, R.; Nguyen, M.; Soriano, F.; Vasquez, N.; Weiss, K.; Welch, B.; Seubert, P.; Schenk, D.; Yednock, T. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease Nat. Med. 2000, 6, 916-919
15. Zhou, Q. H.; Fu, A.; Boado, R. J.; Hui, E. K.-H.; Lu, J. Z.; Pardridge, W. M. Receptor-mediated Abeta amyloid antibody targeting to Alzheimer's disease mouse brain Mol. Pharmaceutics 2011, 8, 280-285
16. Sumbria, R. K.; Zhou, Q.-H.; Hui, E.K.-W.; Lu, J. Z.; Boado, R. J.; Pardridge, W. M. Pharmacokinetics and brain uptake of an IgG-TNF decoy receptor fusion protein following intravenous, intraperitoneal, and subcutaneous administration in mice Mol. Pharmaceutics 2013, 10, 1425-1431
17. Perdivara, I.; Deterding, L.; Moise, A.; Tomer, K. B.; Przybylski, M. Determination of primary structure and microheterogeneity of a β-amyloid plaque-specific antibody using high-performance LC-tandem mass spectrometry Anal. Bioanal. Chem. 2008, 391, 325-336
18. Ly, P. T.; Cai, F.; Song, W. Detection of neuritic plaques in Alzheimer's disease mouse model. J. Visualized Exp. 2011, 53, DOI: 10.3791/2831.
19. Kumar-Singh, S.; Pirici, D.; McGowan, E.; Serneels, S.; Ceuterick, C.; Hardy, J.; Duff, K.; Dickson, D.; Van Broeckhoven, C. Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls Am. J. Pathol. 2005, 167, 527-43
20. Wang, A.; Das, P.; Switzer, R. C.; Golde, T. E.; Jankowsky, J. L. Robust amyloid clearance in a mouse model of Alzheimer's disease provides novel insights into the mechanism of amyloid-β immunotherapy J. Neurosci. 2011, 31, 4124-4136
21. Chishti, M. A.; Yang, D. S.; Janus, C.; Phinney, A. L.; Horne, P.; Pearson, J.; Strome, R.; Zuker, N.; Loukides, J.; French, J.; Turner, S.; Lozza, G.; Grilli, M.; Kunicki, S.; Morissette, C.; Paquette, J.; Gervais, F.; Bergeron, C.; Fraser, P. E.; Carlson, G. A.; George-Hyslop, P. S.; Westaway, D. Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695 J. Biol. Chem. 2001, 276, 21562-21570
22. Racke, M. M.; Boone, L. I.; Hepburn, D. L.; Parsadainian, M.; Bryan, M. T.; Ness, D. K.; Piroozi, K. S.; Jordan, W. H.; Brown, D. D.; Hoffman, W. P.; Holtzman, D. M.; Bales, K. R.; Gitter, B. D.; May, P. C.; Paul, S. M.; DeMattos, R. B. Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid β J. Neurosci. 2005, 25, 629-636
23. Wilcock, D. M.; Alamed, J.; Gottschall, P. E.; Grimm, J.; Rosenthal, A.; Pons, J.; Ronan, V.; Symmonds, K.; Gordon, M. N.; Morgan, D. Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice J. Neurosci. 2006, 26, 5340-5346
24. Jancsó, G.; Domoki, F.; Sántha, P.; Varga, J.; Fischer, J.; Orosz, K.; Penke, B.; Becskei, A.; Dux, M.; Tóth, L. Beta-amyloid (1-42) peptide impairs blood-brain barrier function after intracarotid infusion in rats Neurosci. Lett. 1998, 253, 139-141
25. Su, G. C.; Arendash, G. W.; Kalaria, R. N.; Bjugstad, K. B.; Mullan, M. Intravascular infusions of soluble β-amyloid compromise the blood-brain barrier, activate CNS glial cells and induce peripheral hemorrhage Brain Res. 1999, 818, 105-117
26. Wilcock, D. M.; Colton, C. A. Immunotherapy, vascular pathology, and microhemorrhages in transgenic mice CNS Neurol. Disord. Drug Targets 2009, 8, 50-64
27. Sperling, R.; Salloway, S.; Brooks, D. J.; Tampieri, D.; Barakos, J.; Fox, N. C.; Raskind, M.; Sabbagh, M.; Honig, L. S.; Porsteinsson, A. P.; Lieberburg, I.; Arrighi, H. M.; Morris, K. A.; Lu, Y.; Liu, E.; Gregg, K. M.; Brashear, H. R.; Kinney, G. G.; Black, R.; Grundman, M. Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis Lancet Neurol. 2012, 11, 241-249
28. Ostrowitzki, S.; Deptula, D.; Thurfjell, L.; Barkhof, F.; Bohrmann, B.; Brooks, D. J.; Klunk, W. E.; Ashford, E.; Yoo, K.; Xu, Z. X.; Loetscher, H.; Santarelli, L. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab Arch. Neurol. 2012, 69, 198-207
29. Bard, F.; Fox, M.; Friedrich, S.; Seubert, P.; Schenk, D.; Kinney, G. G.; Yednock, T. Sustained levels of antibodies against Aβ in amyloid-rich regions of the CNS following intravenous dosing in human APP transgenic mice Exp. Neurol. 2012, 238, 38-43
30. Lee, H. J.; Engelhardt, B.; Lesley, J.; Bickel, U.; Pardridge, W. M. Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse J. Pharmacol. Exp. Ther. 2000, 292, 1048-1052
31. Greenblatt, D. J.; Sethy, V. H. Benzodiazepine concentrations in brain directly reflect receptor occupancy: studies of diazepam, lorezepam, and oxazepam Psychopharmacology 1990, 102, 373-378
32. Zhou, Q.-H.; Boado, R. J.; Lu, J. Z.; Hui, E.K.-W.; Pardridge, W. M. Chronic dosing of mice with a transferrin receptor monoclonal antibody-GDNF fusion protein Drug Metab. Dispos. 2011, 39, 1149-1154