A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice

Molecular Neurodegeneration
Ulf NeumannLaura H Jacobson

Abstract

Alzheimer's disease (AD) is the most common form of dementia, the number of affected individuals is rising, with significant impacts for healthcare systems. Current symptomatic treatments delay, but do not halt, disease progression. Genetic evidence points to aggregation and deposition of amyloid-β (Aβ) in the brain being causal for the neurodegeneration and dementia typical of AD. Approaches to target Aβ via inhibition of γ-secretase or passive antibody therapy have not yet resulted in substantial clinical benefits. Inhibition of BACE1 (β-secretase) has proven a challenging concept, but recent BACE1inhibitors can enter the brain sufficiently well to lower Aβ. However, failures with the first clinical BACE1 inhibitors have highlighted the need to generate compounds with appropriate efficacy and safety profiles, since long treatment periods are expected to be necessary in humans. Treatment with NB-360, a potent and brain penetrable BACE-1 inhibitor can completely block the progression of Aβ deposition in the brains of APP transgenic mice, a model for amyloid pathology. We furthermore show that almost complete reduction of Aβ was achieved also in rats and in dogs, suggesting that these findings are translational across species an...Continue Reading

References

Jul 10, 2007·The Journal of Biological Chemistry·Lisa McConlogueSukanto Sinha
Oct 27, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Bo FengSonia M de Morais
Aug 9, 2008·The Journal of Pharmacology and Experimental Therapeutics·Dorothee AbramowskiMatthias Staufenbiel
Dec 1, 2009·Brain Research Reviews·Michael T HenekaAlexei Verkhratsky
Aug 5, 2011·Journal of Neurochemistry·Sabine RabeMatthias Staufenbiel
Nov 18, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Patrick C MayJames E Audia
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Tony Wyss-Coray, Joseph Rogers
Jun 8, 2012·Cold Spring Harbor Perspectives in Medicine·Colin L Masters, Dennis J Selkoe
Mar 13, 2013·Lancet Neurology·Victor L VillemagneUNKNOWN Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group
Mar 27, 2013·Biochimica Et Biophysica Acta·Elizabeth Head
Jun 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Leila RochinGuillaume van Niel
Aug 8, 2013·The International Journal of Neuroscience·M Obulesu, M Jhansilakshmi
Jan 24, 2014·The New England Journal of Medicine·Rachelle S DoodyUNKNOWN Solanezumab Study Group
Jan 24, 2014·The New England Journal of Medicine·Stephen SallowayUNKNOWN Bapineuzumab 301 and 302 Clinical Trial Investigators
Feb 22, 2014·Lancet Neurology·Riqiang Yan, Robert Vassar
Mar 22, 2014·Journal of Neurochemistry·Robert VassarStefan F Lichtenthaler
Apr 8, 2014·Bioorganic & Medicinal Chemistry Letters·Daniel OehlrichHarrie J M Gijsen
Aug 29, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Helmut JacobsenBernd Bohrmann
Sep 18, 2014·Journal of Alzheimer's Disease : JAD·Jun WangJin-Tai Yu
Nov 2, 2014·Toxicologic Pathology·Mark R FieldenRuth Lightfoot-Dunn
Jan 23, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Patrick C MayDustin J Mergott
May 1, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Deepak R ThakkerLisa L Shafer

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Citations

Mar 5, 2016·Frontiers in Aging Neuroscience·Yanfang LiHui Zheng
Mar 18, 2016·Cellular and Molecular Neurobiology·Guillaume van Niel
Oct 30, 2016·Frontiers in Molecular Neuroscience·Stephan A MüllerStefan F Lichtenthaler
Oct 27, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Juliane SchelleStephan A Kaeser
Apr 1, 2017·Expert Opinion on Investigational Drugs·Chris G Parsons, Gerhard Rammes
Jan 14, 2017·Medicinal Research Reviews·Sergey O BachurinAleksey A Ustyugov
Dec 5, 2016·Bioorganic & Medicinal Chemistry Letters·Marek Bajda, Sławomir Filipek
Jul 10, 2018·Annual Review of Neuroscience·Benedikt ZottArthur Konnerth
Aug 5, 2017·The EMBO Journal·Hiroki SasaguriTakaomi C Saido
Sep 19, 2018·EMBO Molecular Medicine·Ulf NeumannCristina Lopez Lopez
Jul 31, 2019·Annals of Neurology·Juliane SchelleMathias Jucker
Mar 19, 2020·International Journal of Molecular Sciences·Christopher D MorroneJoAnne McLaurin
Jul 16, 2016·Translational Neurodegeneration·Riqiang Yan
Aug 5, 2020·EMBO Reports·Vittoria MataforaAngela Bachi
May 10, 2018·The Journal of Experimental Medicine·Ying DuHuaxi Xu
Mar 30, 2016·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Genevieve Evin
Jan 1, 2016·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·S O Bachurin
Sep 1, 2017·British Journal of Pharmacology·Daniela Bumbaca YadavJasvinder K Atwal
Nov 21, 2018·Life Science Alliance·Iryna VoytyukBart De Strooper
Jul 25, 2018·Journal of Alzheimer's Disease : JAD·Morgane PitonAudrey Gabelle
Aug 11, 2018·Frontiers in Aging Neuroscience·Tanja BlumeJochen Herms
Aug 28, 2020·Frontiers in Molecular Neuroscience·Jing ZhaoChunyu Wang
Jul 26, 2017·Proceedings of the National Academy of Sciences of the United States of America·Aylin D KeskinMarc Aurel Busche
Jun 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qiuchen ZhengNoel D Lazo
Jun 24, 2017·Frontiers in Aging Neuroscience·Emiliano Peña-AltamiraBarbara Monti
Jul 28, 2019·Medicinal Research Reviews·Nour M Moussa-PachaTaleb H Al-Tel
Oct 3, 2020·Expert Opinion on Therapeutic Patents·Frederik RomboutsHarrie J M Gijsen
Feb 6, 2021·ACS Chemical Neuroscience·Yu-Chen YenAndrew D Mesecar
Feb 24, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Silvio R MeierStina Syvänen

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Methods Mentioned

BETA
transgenic
BACE
FRET

Software Mentioned

Matrox MIL
ASTORIA , Automated Stored Image Analysis
Sigma Plot
MS Visual Studio
Origin
ImageScope
MicroCal

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