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...
- 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...
- 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...
- Evaluation of TrkB and BDNF transcripts in prefrontal cortex, hippocampus, and striatum from subjects with schizophrenia, bipolar disorder, and major depressive disorderVeronica Reinhart
Neuroscience, Pfizer Inc, Cambridge, MA, USA
Neurobiol Dis 77:220-7. 2015..Novel therapies aimed at improving BDNF-TrkB signaling may therefore have potential to impact on a range of psychiatric disorders. ..
- 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...