Safety, Tolerability, and Changes in Amyloid β Concentrations After Administration of a γ-Secretase Inhibitor in Volunteers

Clinical Neuropharmacology - Tập 28 Số 3 - Trang 126-132 - 2005
Eric Siemers1, Michael Skinner1, Robert A. Dean1, Celedon Gonzales1, Julie Satterwhite1, Martin R. Farlow2, Daniel Ness1, Patrick C. May1
1Lilly Research Laboratories
2Indiana University School of Medicine, Department of Neurology, Indianapolis, Indiana.

Tóm tắt

Từ khóa


Tài liệu tham khảo

Jost, 1995, The natural history of Alzheimers disease: a brain bank study., J Am Geriatr Soc, 43, 1248, 10.1111/j.1532-5415.1995.tb07401.x

Schneider, 2001, Treatment of Alzheimers disease with cholinesterase inhibitors., Clin Geriatr Med, 17, 337, 10.1016/S0749-0690(05)70072-0

Reisberg, 2003, Memantine in moderate-to-severe Alzheimers disease., N Engl J Med, 348, 1333, 10.1056/NEJMoa013128

Tariot, 2004, Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil. A randomized controlled trial., JAMA, 291, 317, 10.1001/jama.291.3.317

Selkoe, 1994, Normal and abnormal biology of the -amyloid precursor protein., Annu Rev Neurosci, 17, 489, 10.1146/annurev.ne.17.030194.002421

Schenk, 1995, Therapeutic approaches related to amyloid-beta peptide and Alzheimers disease., J Med Chem, 38, 4141, 10.1021/jm00021a001

Selkoe, 1998, The cell biology of beta-amyloid precursor protein and presenilin in Alzheimers disease., Trends Cell Biol, 8, 447, 10.1016/S0962-8924(98)01363-4

Bayer, 2001, Key factors in Alzheimers disease: beta-amyloid precursor protein processing, metabolism and intraneuronal transport., Brain Pathol, 11, 1, 10.1111/j.1750-3639.2001.tb00376.x

Selkoe, 1996, Cell biology of the beta-amyloid protein and the genetics of Alzheimers disease., Cold Spring Harb Symp Quant Biol, 61, 587, 10.1101/SQB.1996.061.01.059

Scheuner, 1996, Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimers disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimers disease., Nat Med, 2, 864, 10.1038/nm0896-864

Wolfe, 2001, The role of presenilins in gamma-secretase activity., J Biol Chem, 276, 5413, 10.1074/jbc.R000026200

Corder, 1993, Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimers disease in late onset families., Science, 261, 921, 10.1126/science.8346443

Corder, 1994, Protective effect of apolipoprotein E type 2 allele for late onset alzheimer disease., Nat Genet, 7, 180, 10.1038/ng0694-180

Reiman, 1996, Preclinical evidence of Alzheimers disease in persons homozygous for the 4 allele for apolipoprotein E., N Engl J Med, 334, 752, 10.1056/NEJM199603213341202

Saunders, 1993, Association of apolipoprotein E allele 4 with late-onset familial and sporadic Alzheimers disease., Neurology, 43, 1467, 10.1212/WNL.43.8.1467

Romas, 1999, APOE genotype, plasma lipids, lipoproteins, and AD in community elderly., Neurology, 53, 517, 10.1212/WNL.53.3.517

Holtzman, 2001, Role of apoe/Abeta interactions in the pathogenesis of Alzheimers disease and cerebral amyloid angiopathy., J Mol Neurosci, 17, 147, 10.1385/JMN:17:2:147

Games, 1995, Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein., Nature, 373, 523, 10.1038/373523a0

Gitter, 2004, Stereoselective inhibition of amyloid beta peptide secretion by LY450139, a novel functional gamma secretase inhibitor., Neurobiol Aging, 25, 571, 10.1016/S0197-4580(04)81897-9

Ness, 2004, Reduced -amyloid burden, increased C-99 concentrations and evaluation of neuropathology in the brains of PDAPP mice given LY450139 dihydrate daily by gavage for 5 months., Neurobiol Aging, 25, 238, 10.1016/S0197-4580(04)80800-5

Siemers, 2004, Safety, tolerability, and changes in plasma and cerebrospinal fluid amyloid beta concentrations after administration of a functional gamma-secretase inhibitor in healthy volunteers., Neurobiol Aging, 25, 569, 10.1016/S0197-4580(04)81891-8

Siemers, 2004, Effect of LY450139, a functional -secretase inhibitor, on plasma and cerebrospinal fluid concentrations of A and cognitive functioning in patients with mild to moderate Alzheimers disease., Neurology, 62, A174

Wong, 2004, Chronic treatment with the -secretase inhibitor LY-411,575 inhibits -amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation., J Biol Chem, 279, 12876, 10.1074/jbc.M311652200

Searfoss, 2003, Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional -secretase inhibitor., J Biol Chem, 278, 46107, 10.1074/jbc.M307757200

Kimberly, 2003, Identity and function of -secretase., J Neurosci Res, 74, 353, 10.1002/jnr.10736

De Strooper, 1999, A presenilin-1-dependent -secretase-like protease mediates release of Notch intracellular domain., Nature, 398, 518, 10.1038/19083

Zhang, 2000, Presenilins are required for gamma-secretase cleavage of -APP and transmembrane cleavage of Notch-1., Nat Cell Biol, 2, 463, 10.1038/35017108

Hartmann, 2001, Implication of APP secretases in notch signaling., J Mol Neurosci, 17, 171, 10.1385/JMN:17:2:171

Micchelli, 2003, Gamma-secretase/presenilin inhibitors for Alzheimers disease phenocopy Notch mutations in Drosophila., FASEB J, 17, 79, 10.1096/fj.02-0394fje

Yang, 2001, Requirement of math 1 for secretory cell lineage commitment in the mouse intestine., Science, 294, 2155, 10.1126/science.1065718

Hyslop, 2004, Reduction in A-beta(1-40) and A-beta(1-42) in CSF and plasma in the beagle dog following acute oral dosing of the gamma secretase inhibitor, LY450139., Neurobiol Aging, 25, 147, 10.1016/S0197-4580(04)80493-7

May, 2004, Multi-compartmental pharmaco-dynamic assessment of the functional gamma-secretase inhibitor LY450139 in PDAPP transgenic mice and non-transgenic mice., Neurobiol Aging, 25, 65, 10.1016/S0197-4580(04)80220-3

Shibata, 2000, Clearance of Alzheimers amyloid-1-40 peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier., J Clin Invest, 106, 1489, 10.1172/JCI10498

DeMattos, 2001, Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimers disease., Proc Natl Acad Sci U S A, 98, 8850, 10.1073/pnas.151261398

Kanai, 1998, Longitudinal study of cerebrospinal fluid levels of tau, A1-40, and A1-42(43) in Alzheimers disease: a study in Japan., Ann Neurol, 44, 17, 10.1002/ana.410440108

Andreasen, 1999, Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimers disease in patients with mild cognitive impairment., Neurosci Lett, 273, 5, 10.1016/S0304-3940(99)00617-5

Jensen, 1999, Cerebrospinal fluid Abeta42 is increased early in sporadic Alzheimers disease and declines with disease progression., Ann Neurol, 45, 504, 10.1002/1531-8249(199904)45:4<504::AID-ANA12>3.0.CO;2-9

Graff-Radford, 2003, Longitudinal analysis of plasma A42 in subjects progressing from normal through mild cognitive impairment to Alzheimers disease., Neurology, 60, A245

Mehta, 2000, Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease., Arch Neurol, 57, 100, 10.1001/archneur.57.1.100

Mayeux, 2003, Plasma A40 and A42 and Alzheimers disease. Relation to age, mortality and risk., Neurology, 61, 1185, 10.1212/01.WNL.0000091890.32140.8F

Farlow, 2002, Basal A levels in plasma and cerebrospinal fluid of healthy subjects and patients with Alzheimer disease., Neurology, 58, A485

Hock, 2003, Treatment with the selective muscarinic m1 agonist talsaclidine decreases cerebrospinal fluid levels of Abeta 42 in patients with Alzheimers disease., Amyloid, 10, 1, 10.3109/13506120308995249

Nitsch, 2000, The selective muscarinic M1 agonist AF102B decreases levels of total Abeta in cerebrospinal fluid of patients with Alzheimers disease., Ann Neurol, 48, 913, 10.1002/1531-8249(200012)48:6<913::AID-ANA12>3.0.CO;2-S