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Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease.
Ayalon G, Lee SH, Adolfsson O, Foo-Atkins C, Atwal JK, Blendstrup M, Booler H, Bravo J, Brendza R, Brunstein F, Chan R, Chandra P, Couch JA, Datwani A, Demeule B, DiCara D, Erickson R, Ernst JA, Foreman O, He D, Hötzel I, Keeley M, Kwok MCM, Lafrance-Vanasse J, Lin H, Lu Y, Luk W, Manser P, Muhs A, Ngu H, Pfeifer A, Pihlgren M, Rao GK, Scearce-Levie K, Schauer SP, Smith WB, Solanoy H, Teng E, Wildsmith KR, Bumbaca Yadav D, Ying Y, Fuji RN, Kerchner GA. Ayalon G, et al. Sci Transl Med. 2021 May 12;13(593):eabb2639. doi: 10.1126/scitranslmed.abb2639. Sci Transl Med. 2021. PMID: 33980574 Clinical Trial.
A therapeutic antibody targeting BACE1 inhibits amyloid-β production in vivo.
Atwal JK, Chen Y, Chiu C, Mortensen DL, Meilandt WJ, Liu Y, Heise CE, Hoyte K, Luk W, Lu Y, Peng K, Wu P, Rouge L, Zhang Y, Lazarus RA, Scearce-Levie K, Wang W, Wu Y, Tessier-Lavigne M, Watts RJ. Atwal JK, et al. Sci Transl Med. 2011 May 25;3(84):84ra43. doi: 10.1126/scitranslmed.3002254. Sci Transl Med. 2011. PMID: 21613622
Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations.
Sheng Z, Zhang S, Bustos D, Kleinheinz T, Le Pichon CE, Dominguez SL, Solanoy HO, Drummond J, Zhang X, Ding X, Cai F, Song Q, Li X, Yue Z, van der Brug MP, Burdick DJ, Gunzner-Toste J, Chen H, Liu X, Estrada AA, Sweeney ZK, Scearce-Levie K, Moffat JG, Kirkpatrick DS, Zhu H. Sheng Z, et al. Sci Transl Med. 2012 Dec 12;4(164):164ra161. doi: 10.1126/scitranslmed.3004485. Sci Transl Med. 2012. PMID: 23241745
Mechanistic pharmacokinetic-pharmacodynamic modeling of BACE1 inhibition in monkeys: development of a predictive model for amyloid precursor protein processing.
Liu X, Wong H, Scearce-Levie K, Watts RJ, Coraggio M, Shin YG, Peng K, Wildsmith KR, Atwal JK, Mango J, Schauer SP, Regal K, Hunt KW, Thomas AA, Siu M, Lyssikatos J, Deshmukh G, Hop CE. Liu X, et al. Drug Metab Dispos. 2013 Jul;41(7):1319-28. doi: 10.1124/dmd.112.050864. Epub 2013 Apr 12. Drug Metab Dispos. 2013. PMID: 23584887
Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier.
Couch JA, Yu YJ, Zhang Y, Tarrant JM, Fuji RN, Meilandt WJ, Solanoy H, Tong RK, Hoyte K, Luk W, Lu Y, Gadkar K, Prabhu S, Ordonia BA, Nguyen Q, Lin Y, Lin Z, Balazs M, Scearce-Levie K, Ernst JA, Dennis MS, Watts RJ. Couch JA, et al. Sci Transl Med. 2013 May 1;5(183):183ra57, 1-12. doi: 10.1126/scitranslmed.3005338. Sci Transl Med. 2013. PMID: 23636093
Dual leucine zipper kinase is required for excitotoxicity-induced neuronal degeneration.
Pozniak CD, Sengupta Ghosh A, Gogineni A, Hanson JE, Lee SH, Larson JL, Solanoy H, Bustos D, Li H, Ngu H, Jubb AM, Ayalon G, Wu J, Scearce-Levie K, Zhou Q, Weimer RM, Kirkpatrick DS, Lewcock JW. Pozniak CD, et al. J Exp Med. 2013 Nov 18;210(12):2553-67. doi: 10.1084/jem.20122832. Epub 2013 Oct 28. J Exp Med. 2013. PMID: 24166713 Free PMC article.
Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models.
Patel S, Cohen F, Dean BJ, De La Torre K, Deshmukh G, Estrada AA, Ghosh AS, Gibbons P, Gustafson A, Huestis MP, Le Pichon CE, Lin H, Liu W, Liu X, Liu Y, Ly CQ, Lyssikatos JP, Ma C, Scearce-Levie K, Shin YG, Solanoy H, Stark KL, Wang J, Wang B, Zhao X, Lewcock JW, Siu M. Patel S, et al. J Med Chem. 2015 Jan 8;58(1):401-18. doi: 10.1021/jm5013984. Epub 2014 Oct 23. J Med Chem. 2015. PMID: 25341110
Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman primates.
Yu YJ, Atwal JK, Zhang Y, Tong RK, Wildsmith KR, Tan C, Bien-Ly N, Hersom M, Maloney JA, Meilandt WJ, Bumbaca D, Gadkar K, Hoyte K, Luk W, Lu Y, Ernst JA, Scearce-Levie K, Couch JA, Dennis MS, Watts RJ. Yu YJ, et al. Sci Transl Med. 2014 Nov 5;6(261):261ra154. doi: 10.1126/scitranslmed.3009835. Sci Transl Med. 2014. PMID: 25378646
80 results