Profile of gantenerumab and its potential in the treatment of Alzheimer's disease

Drug Design, Development and Therapy

Volumn 7, Issue , 2013, Pages 1359-1364

  Novakovic, Dijana ^a   Feligioni, Marco ^b   Scaccianoce, Sergio ^a   Caruso, Alessandra ^a   Piccinin, Sonia ^b   Schepisi, Chiara ^a,b   Errico, Francesco ^c   Mercuri, Nicola B ^d   Nicoletti, Ferdinando ^a,e   Nisticò, Robert ^a,d  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b EUROPEAN BRAIN RESEARCH INSTITUTE   (Italy)

^c CEINGE BIOTECNOLOGIE AVANZATE   (Italy)

^d IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^e Istituto di Ricerca e Cura a Carattere Scientifico Neuromed   (Italy)

Author keywords

Alzheimer's disease; Amyloid ; Clinical trials; Gantenerumab; Monoclonal antibody

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN ANTIBODY; APOLIPOPROTEIN E; BAPINEUZUMAB; CRENEZUMAB; GANTENERUMAB; GSK 933776A; HUCAL; MONOCLONAL ANTIBODY; PLACEBO; PONEZUMAB; SOLANEZUMAB; UNCLASSIFIED DRUG;

ACTIVE IMMUNIZATION; ALZHEIMER DISEASE; AMYLOID PLAQUE; AREA UNDER THE CURVE; COGNITIVE DEFECT; DOSE RESPONSE; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG HALF LIFE; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG SPECIFICITY; DRUG TARGETING; DRUG TOLERABILITY; HUMAN; MAXIMUM PLASMA CONCENTRATION; NEUROPATHOLOGY; NONHUMAN; PASSIVE IMMUNIZATION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POSITRON EMISSION TOMOGRAPHY; PROTEIN TARGETING; REVIEW;

ALZHEIMER'S DISEASE; AMYLOID-Β; CLINICAL TRIALS; GANTENERUMAB; MONOCLONAL ANTIBODY;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; ANTIBODIES, MONOCLONAL; BRAIN; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DRUG EVALUATION, PRECLINICAL; HUMANS;

EID: 84887763795     PISSN: 11778881     EISSN: None     Source Type: Journal    
DOI: 10.2147/DDDT.S53401     Document Type: Review

References (46)

1. Thies W, Bleiler L; Alzheimer's Association. 2013 Alzheimer's disease facts and figures. Alzheimers Dement. 2013;9(2):208-245.
2. Selkoe DJ. Alzheimer's disease is a synaptic failure. Science. 2002;298(5594):789-791.
3. Francis PT, Nordberg A, Arnold SE. A preclinical view of cholinesterase inhibitors in neuroprotection: do they provide more than symptomatic benefits in Alzheimer's disease? Trends Pharmacol Sci. 2005;26(2): 104-111.
4. Zhou J, Fu Y, Tang XC. Huperzine A and donepezil protect rat pheochromocytoma cells against oxygen-glucose deprivation. Neurosci Lett. 2001;306(1-2):53-56.
5. Wang ZF, Zhou J, Tang XC. Huperzine B protects rat pheochromocytoma cells against oxygen-glucose deprivation-induced injury. Acta Pharmacol Sin. 2002;23(12):1193-1198.
6. Tabet N. Acetylcholinesterase inhibitors for Alzheimer's disease: anti-inflammatories in acetylcholine clothing! Age Ageing. 2006;35(4): 336-338.
7. Shytle RD, Mori T, Townsend K, et al. Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. J Neurochem. 2004;89(2):337-343.
8. Pollak Y, Gilboa A, Ben-Menachem O, Ben-Hur T, Soreq H, Yirmiya R. Acetylcholinesterase inhibitors reduce brain and blood interleukin-1beta production. Ann Neurol. 2005;57(5):741-745.
9. Xiao XQ, Wang R, Tang XC. Huperzine A and tacrine attenuate beta-amyloid peptide-induced oxidative injury. J Neurosci Res. 2000;61(5):564-569.
10. Klugman A, Naughton DP, Isaac M, Shah I, Petroczi A, Tabet N. Antioxidant enzymatic activities in Alzheimer's disease: the relationship to acetylcholinesterase inhibitors. J Alzheimers Dis. 2012;30(3): 467-474.
11. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002; 297(5580):353-356.
12. Findeis MA. Peptide inhibitors of beta amyloid aggregation. Curr Top Med Chem. 2002;2(4):417-423.
13. Nakagami Y, Nishimura S, Murasugi T, et al. A novel compound RS-0466 reverses beta-amyloid-induced cytotoxicity through the Akt signaling pathway in vitro. Eur J Pharmacol. 2002;457(1):11-17.
14. Nakagami Y, Nishimura S, Murasugi T, et al. A novel beta-sheet breaker, RS-0406, reverses amyloid beta-induced cytotoxicity and impairment of long-term potentiation in vitro. Br J Pharmacol. 2002;137(5):676-682.
15. Walsh DM, Klyubin I, Shankar GM, et al. The role of cell-derived oligomers of Abeta in Alzheimer's disease and avenues for therapeutic intervention. Biochem Soc Trans. 2005;33(Pt 5):1087-1090.
16. Toyn JH, Rowley A, Matsuoka Y, Tomita T, Imbimbo BP. γ-Secretase Pharmacology: What Pharmacology Will Work for Alzheimer's Disease? Int J Alzheimers Dis. 2013;2013:849128.
17. Leissring MA. Proteolytic degradation of the amyloid beta-protein: the forgotten side of Alzheimer's disease. Curr Alzheimer Res. 2006;3(5): 431-435.
18. Selkoe DJ. Clearing the brain's amyloid cobwebs. Neuron. 2001; 32(2):177-180.
19. Schenk D. Amyloid-beta immunotherapy for Alzheimer's disease: the end of the beginning. Nat Rev Neurosci. 2002;3(10):824-828.
20. Senior K. Dosing in phase II trial of Alzheimer's vaccine suspended. Lancet Neurol. 2002;1(1):3.
21. Kerchner GA, Boxer AL. Bapineuzumab. Expert Opin Biol Ther. 2010;10(7):1121-1130.
22. Samadi H, Sultzer D. Solanezumab for Alzheimer's disease. Expert Opin Biol Ther. 2011;11(6):787-798.
23. Vellas B, Carrillo MC, Sampaio C, et al; EU/US/CTAD Task Force Members. Designing drug trials for Alzheimer's disease: what we have learned from the release of the phase III antibody trials: a report from the EU/US/CTAD Task Force. Alzheimers Dement. 2013;9(4):438-444.
24. Eli Lilly and Company. Lilly provides update on next stepsfor Solanezumab; December 12, 2012. Available from: http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=726309. Accessed October 20, 2013.
25. Bohrmann B, Baumann K, Benz J, et al. Gantenerumab: a novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β. J Alzheimers Dis. 2012;28(1):49-69.
26. Koenigsknecht-Talboo J, Meyer-Luehmann M, Parsadanian M, et al. Rapid microglial response around amyloid pathology after systemic anti-Abeta antibody administration in PDAPP mice. J Neurosci. 2008;28(52):14156-14164.
27. Dolman NP, Troop HM, More JC, et al. Synthesis and pharmacology of willardiine derivatives acting as antagonists of kainate receptors. J Med Chem. 2005;48(24):7867-7881.
28. Dargan SL, Clarke VR, Alushin GM, et al. ACET is a highly potent and specific kainate receptor antagonist: characterisation and effects on hippocampal mossy fibre function. Neuropharmacology. 2009;56(1): 121-130.
29. Nisticò R, Pignatelli M, Piccinin S, Mercuri NB, Collingridge G. Targeting synaptic dysfunction in Alzheimer's disease therapy. Mol Neurobiol. 2012;46(3):572-587.
30. Errico F, Nisticò R, Palma G, et al. Increased levels of d-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility. Mol Cell Neurosci. 2008;37(2):236-246.
31. Errico F, Nisticò R, Napolitano F, et al. Increased D-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice. Neurobiol Aging. 2011;32(12):2229-2243.
32. Errico F, Nisticò R, Napolitano F, et al. Persistent increase of D-aspartate in D-aspartate oxidase mutant mice induces a precocious hippocampal age-dependent synaptic plasticity and spatial memory decay. Neurobiol Aging. 2011;32(11):2061-2074.
33. Molinaro P, Viggiano D, Nisticò R, et al. Na+-Ca2+ exchanger (NCX3) knock-out mice display an impairment in hippocampal long-term potentiation and spatial learning and memory. J Neurosci. 2011;31(20): 7312-7321.
34. Bonito-Oliva A, Pignatelli M, Spigolon G, et al. Cognitive Impairment and Dentate Gyrus Synaptic Dysfunction in Experimental Parkinsonism. Biol Psychiatry. Epub March 28, 2013.
35. Pignatelli M, Vollmayr B, Richter SH, et al. Enhanced mGlu5-receptor dependent long-term depression at the Schaffer collateral-CA1 synapse of congenitally learned helpless rats. Neuropharmacology. 2013;66: 339-347.
36. Pignatelli M, Feligioni M, Piccinin S, Molinaro G, Nicoletti F, Nisticò R. Synaptic plasticity as a therapeutic target in the treatment of autism-related single-gene disorders. Curr Pharm Des. Epub February 13, 2013.
37. Nisticò R, Mango D, Mandolesi G, et al. Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis. PLoS One. 2013;8(1):e54666.
38. Balducci C, Mehdawy B, Mare L, et al. The γ-secretase modulator CHF5074 restores memory and hippocampal synaptic plasticity in plaque-free Tg2576 mice. J Alzheimers Dis. 2011;24(4):799-816.
39. La Rosa LR, Matrone C, Ferraina C, et al. Age-related changes of hippocampal synaptic plasticity in AβPP-null mice are restored by NGF through p75 NTR. J Alzheimers Dis. 2013;33(1):265-272.
40. Knobloch M, Farinelli M, Konietzko U, Nitsch RM, Mansuy IM. Abeta oligomer-mediated long-term potentiation impairment involves protein phosphatase 1-dependent mechanisms. J Neurosci. 2007; 27(29):7648-7653.
41. Zago W, Buttini M, Comery TA, et al. Neutralization of soluble, synaptotoxic amyloid β species by antibodies is epitope specific. J Neurosci. 2012;32(8):2696-2702.
42. Dodart JC, Bales KR, Gannon KS, et al. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nat Neurosci. 2002;5(5):452-457.
43. Ostrowitzki S, Deptula D, Thurfjell L, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69(2):198-207.
44. Boche D, Nicoll JA. The role of the immune system in clearance of Abeta from the brain. Brain Pathol. 2008;18(2):267-278.
45. Nicoll JA, Barton E, Boche D, et al. Abeta species removal after abeta42 immunization. J Neuropathol Exp Neurol. 2006;65(11): 1040-1048.
46. Giuffrida ML, Caraci F, Pignataro B, et al. Beta-amyloid monomers are neuroprotective. J Neurosci. 2009;29(34):10582-10587.