Thomas A Lanz
Affiliation: Pfizer Global Research and Development
- Solid-phase extraction enhances detection of beta-amyloid peptides in plasma and enables Abeta quantification following passive immunization with Abeta antibodiesThomas A Lanz
CNS Biology, Pfizer Inc, Groton, CT 06340, United States
J Neurosci Methods 169:16-22. 2008..Given the availability of a variety of SPE matrices, we hypothesize that these methods could facilitate plasma antigen retrieval using multiple therapeutic antibody approaches...
- Robust changes in expression of brain-derived neurotrophic factor (BDNF) mRNA and protein across the brain do not translate to detectable changes in BDNF levels in CSF or plasmaThomas A Lanz
Pfizer Global Research and Development, Groton, CT 06340, USA
Biomarkers 17:524-31. 2012..Thus, while deficits in BDNF signaling have been implicated in a number of diseases, these data suggest that extracellular concentrations of BDNF may not be a facile biomarker for changes in neurons...
- Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014Thomas A Lanz
Neuroscience Research Unit, Pfizer, Inc, Groton, CT 06340, USA
J Pharmacol Exp Ther 334:269-77. 2010..Potency at Abeta relative to Notch-related endpoints in vitro and in vivo suggests that a therapeutic index can be achieved with this compound...
- Peripheral elevation of IGF-1 fails to alter Abeta clearance in multiple in vivo modelsThomas A Lanz
CNS Discovery, Pfizer, Inc, Eastern Point Road, Groton, CT 06340, United States
Biochem Pharmacol 75:1093-103. 2008....
- Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139Thomas A Lanz
Pfizer, Inc, Eastern Point Rd, MS 8220 4183, Groton, CT 06340, USA
J Pharmacol Exp Ther 319:924-33. 2006..These results suggest that LY-450139 modulates the gamma-secretase complex, eliciting Abeta lowering at high concentrations but Abeta elevation at low concentrations...
- Demonstration of a common artifact in immunosorbent assays of brain extracts: development of a solid-phase extraction protocol to enable measurement of amyloid-beta from wild-type rodent brainThomas A Lanz
CNS Biology, Pfizer Inc, MS 8220 4183, Eastern Point Road, Groton, CT 06340, USA
J Neurosci Methods 157:71-81. 2006..This isolation method eliminates non-specific binding components from brain extracts and allows for accurate quantitation and robust detection of multiple Abeta peptides in extracts from wild-type animals...
- Studies of Abeta pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azThomas A Lanz
Pfizer Inc, Eastern Point Road, MS 8220 4183, Groton, CT 06340, USA
J Pharmacol Exp Ther 309:49-55. 2004..Overall, Abeta in the CSF and not plasma seems to be a better biomarker of brain Abeta reduction; however, the time course of Abeta changes needs to be established in clinical studies...
- Design, synthesis, and in vivo characterization of a novel series of tetralin amino imidazoles as γ-secretase inhibitors: discovery of PF-3084014Michael A Brodney
Neuroscience Medicinal Chemistry, Pfizer PharmaTherapeutics Research and Development, Eastern Point Road, Groton, CT 06340, USA
Bioorg Med Chem Lett 21:2637-40. 2011..Optimization of the FTOC to plasma concentrations at the brain Aβ EC(50) lead to the identification of compound 14f (PF-3084014) which was selected for clinical development...
- Lack of specific amyloid-beta(1-42) suppression by nonsteroidal anti-inflammatory drugs in young, plaque-free Tg2576 mice and in guinea pig neuronal culturesThomas A Lanz
Department of Neurobiology, Pfizer, Inc, Kalamazoo, Michigan, USA
J Pharmacol Exp Ther 312:399-406. 2005..The divergence of the present data from published reports raises the need to examine the conditions necessary to perceive selective Abeta(1-42) reduction by NSAIDs in neuronal tissue...
- Diamide amino-imidazoles: a novel series of γ-secretase inhibitors for the treatment of Alzheimer's diseaseMichael A Brodney
Neuroscience Medicinal Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
Bioorg Med Chem Lett 21:2631-6. 2011..The therapeutic index between Aβ reductions and changes in B-cell populations were studied for compound 10 h...
- Structural basis of C-terminal β-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer's diseaseSherry L La Porte
Rinat, Pfizer Inc, South San Francisco, CA 94080, USA
J Mol Biol 421:525-36. 2012..These findings provide novel structural insights into the in vivo conformation of the C-terminus of Aβ40 and the brain Aβ-lowering efficacy that we observed following administration of ponezumab in transgenic mouse models...
- Chronic suppression of phosphodiesterase 10A alters striatal expression of genes responsible for neurotransmitter synthesis, neurotransmission, and signaling pathways implicated in Huntington's diseaseRobin J Kleiman
Neuroscience Research Unit, Eastern Point Road, Pfizer Global Research and Development, Groton, CT 06379, USA
J Pharmacol Exp Ther 336:64-76. 2011..The observed changes in signaling and gene expression are predicted to provide neuroprotective effects in models of Huntington's disease...
- The gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester reduces A beta levels in vivo in plasma and cerebrospinal fluid in young (plaque-free) and aged (plaque-bearing) Tg2576 miceThomas A Lanz
Department of Neurobiology, Pharmacia Corporation, 301 Henrietta St, Kalamazoo, MI 49007, USA
J Pharmacol Exp Ther 305:864-71. 2003..We conclude that CSF and plasma A beta may offer a clinically applicable, mechanism-based biomarker for inhibitors of A beta production...