Profiling the dynamics of CSF and plasma Aβ reduction after treatment with JNJ-54861911, a potent oral BACE inhibitor

Alzheimer's and Dementia: Translational Research and Clinical Interventions

Volumn 2, Issue 3, 2016, Pages 202-212

  Timmers, Maarten ^a,b   Van Broeck, Bianca ^a   Ramael, Steven ^c   Slemmon, John ^a   De Waepenaert, Katja ^a   Russu, Alberto ^a   Bogert, Jennifer ^d   Stieltjes, Hans ^a   Shaw, Leslie M ^e   Engelborghs, Sebastiaan ^b,f   Moechars, Dieder ^a   Mercken, Marc ^a   Liu, Enchi ^a   Sinha, Vikash ^d   Kemp, John ^a   Van Nueten, Luc ^a   Tritsmans, Luc ^a   Streffer, Johannes Rolf ^a,b  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^b UNIVERSITY OF ANTWERP   (Belgium)

^c SGS Life Science Services   (Belgium)

^d JANSSEN RESEARCH AND DEVELOPMENT   (United States)

^e UNIVERSITY OF PENNSYLVANIA   (United States)

^f Memory Clinic   (Belgium)

Author keywords

Alzheimer's disease; Amyloid ; BACE inhibitors; BACE1; JNJ 54861911; secretase enzyme

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; APOLIPOPROTEIN E4; BETA SECRETASE 1; BETA SECRETASE INHIBITOR; JNJ 54861911; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; BACKACHE; BLOOD SAMPLING; CEREBROSPINAL FLUID ANALYSIS; COHORT ANALYSIS; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; DRUG URINE LEVEL; ENZYME INHIBITION; FEMALE; HEADACHE; HUMAN; MALE; PHARMACODYNAMICS; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN CEREBROSPINAL FLUID LEVEL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE;

EID: 84989316493     PISSN: None     EISSN: 23528737     Source Type: Journal    
DOI: 10.1016/j.trci.2016.08.001     Document Type: Article

References (31)

1. [1] Morris, J.C., Price, J.L., Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage Alzheimer's disease. J Mol Neurosci 17 (2001), 101–118.
2. [2] Sperling, R., Mormino, E., Johnson, K., The evolution of preclinical Alzheimer's disease: implications for prevention trials. Neuron 84 (2014), 608–622.
3. [3] Hardy, J.A., Higgins, G.A., Alzheimer's disease: the amyloid cascade hypothesis. Science 256 (1992), 184–185.
4. [4] Karran, E., Mercken, M., De Strooper, B., The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10 (2011), 698–712.
5. [5] Sinha, S., Anderson, J.P., Barbour, R., Basi, G.S., Caccavello, R., Davis, D., et al. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature 402 (1999), 537–540.
6. [6] Vassar, R., Bennett, B.D., Babu-Khan, S., Kahn, S., Mendiaz, E.A., Denis, P., et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286 (1999), 735–741.
7. [7] Mattsson, N., Rajendran, L., Zetterberg, H., Gustavsson, M., Andreasson, U., Olsson, M., et al. BACE1 inhibition induces a specific cerebrospinal fluid beta-amyloid pattern that identifies drug effects in the central nervous system. PLoS One, 7, 2012, e31084.
8. [8] Alexander, R., Budd, S., Russell, M., Kugler, A., Cebers, G., Ye, N., et al. AZD3293 A novel BACE1 inhibitor: safety, tolerability, and effects on plasma and CSF Aβ peptides following single- and multiple-dose administration. Neurobiol Aging, 35, 2014, S2.
9. [9] Forman, M., Kleijn, H.-J., Dockendorf, M., Palcza, J., Tseng, J., Canales, C., et al. The novel BACE inhibitor MK-8931 dramatically lowers CSF beta-amyloid in patients with mild-to-moderate Alzheimer's disease. Alzheimers Dement, 9, 2013, P139.
10. [10] Forman, M., Palcza, J., Tseng, J., Leempoels, J., Ramael, S., Han, D., et al. The novel BACE inhibitor MK-8931 dramatically lowers cerebrospinal fluid Aβ peptides in healthy subjects following single- and multiple-dose administration. Alzheimers Dement, 8, 2012, P704.
11. [11] Lai, R., Albala, B., Kaplow, J.M., Aluri, J., Yen, M., Satlin, A., First-in-human study of E2609, a novel BACE1 inhibitor, demonstrates prolonged reductions in plasma beta-amyloid levels after single dosing. Alzheimers Dement, 8, 2012, P96.
12. [12] Lai R AB, Kaplow JM, Majid O, Matijevic M, Aluri J, Satlin A. Novel BACE1 inhibitor E2609 reduces plasma and CSF amyloid in health subjects after 14 days oral administration. The 11th International Conference On Alzheimer's & Parkinson's Diseases. Florence, Italy 2013.
13. [13] Vassar, R., BACE1 inhibitor drugs in clinical trials for Alzheimer's disease. Alzheimers Res Ther, 6, 2014, 89.
14. [14] Van Broeck, B., Timmers, M., Ramael, S., Bogert, J., Shaw, L.M., Mercken, M., et al. Impact of frequent CSF sampling on Ab levels: systematic approach to reveal influencing factors. Alzheimers Res Ther, 8, 2016, 21.
15. [15] Favis, R., Gerry, N.P., Cheng, Y.W., Barany, F., Applications of the universal DNA microarray in molecular medicine. Methods Mol Med 114 (2005), 25–58.
16. [16] Timmerman, P., White, S., McDougall, S., Kall, M.A., Smeraglia, J., Fjording, M.S., et al. Tiered approach into practice: scientific validation for chromatography-based assays in early development-a recommendation from the European Bioanalysis Forum. Bioanalysis 7 (2015), 2387–2398.
17. [17] Struyfs, H., Van Broeck, B., Timmers, M., Fransen, E., Sleegers, K., Van Broeckhoven, C., et al. Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-beta Isoforms for Early and Differential Dementia Diagnosis. J Alzheimers Dis 45 (2015), 813–822.
18. [18] Van Broeck, B., Borgers, M., Meulders, G., Hermans, B., Dhuyvetter, D., Borghys, H., et al. Simultaneous evaluation of Aß1-37/38/40/42 levels after treatment with secretase inhibitors and modulators using a novel immunoassay. Neurodegener Dis, 11, 2013.
19. [19] Lewczuk, P., Kamrowski-Kruck, H., Peters, O., Heuser, I., Jessen, F., Popp, J., et al. Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer's disease: a multicenter study. Mol Psychiatry 15 (2010), 138–145.
20. [20] Shaw, L.M., Vanderstichele, H., Knapik-Czajka, M., Figurski, M., Coart, E., Blennow, K., et al. Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI. Acta Neuropathol 121 (2011), 597–609.
21. [21] Dean, R., Shaw, L.M., Waligorska, T.W., Korecka, M., Figurski, M., Trojanowski, J.Q., et al. Inclusion of patients with Alzheimer's disease pathology in solanezumab expedition 3 using florbetapir pet imaging or inno-bia alzbio3 CSF Aβ1-42. Alzheimers Dement, 10, 2014, P811.
22. [22] Ghosh, A.K., Brindisi, M., Tang, J., Developing beta-secretase inhibitors for treatment of Alzheimer's disease. J Neurochem 120 (2012), 71–83.
23. [23] Ohno, M., Sametsky, E.A., Younkin, L.H., Oakley, H., Younkin, S.G., Citron, M., et al. BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Neuron 41 (2004), 27–33.
24. [24] Thakker, D.R., Sankaranarayanan, S., Weatherspoon, M.R., Harrison, J., Pierdomenico, M., Heisel, J.M., et al. Centrally Delivered BACE1 Inhibitor Activates Microglia, and Reverses Amyloid Pathology and Cognitive Deficit in Aged Tg2576 Mice. J Neurosci 35 (2015), 6931–6936.
25. [25] Jonsson, T., Atwal, J.K., Steinberg, S., Snaedal, J., Jonsson, P.V., Bjornsson, S., et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488 (2012), 96–99.
26. [26] Martenyi, F., Dean, R.A., Lowe, S., Nakano, M., Monk, S., Willis, B.A., et al. BACE inhibitor LY2886721 safety and central and peripheral PK and PD in healthy subjects (HSs). Alzheimers Dement 8 (2012), P583–P584.
27. [27] Mawuenyega, K.G., Kasten, T., Sigurdson, W., Bateman, R.J., Amyloid-beta isoform metabolism quantitation by stable isotope-labeled kinetics. Anal Biochem 440 (2013), 56–62.
28. [28] Dobrowolska, J.A., Michener, M.S., Wu, G., Patterson, B.W., Chott, R., Ovod, V., et al. CNS amyloid-beta, soluble APP-alpha and -beta kinetics during BACE inhibition. J Neurosci 34 (2014), 8336–8346.
29. [29] Höglund, K., Salter, H., Zetterberg, H., Andreason, U., Olsson, T., Alexander, R., et al. Monitoring the soluble amyloid precursor protein alpha (sappa) and beta (sappb) fragments in plasma and CSF from healthy individuals treated with bace inhibitor AZD3293 in a multiple ascending dose study: Pharmacokinetic and pharmacodynamic correlate. Alzheimers Dement, 10, 2014, P447.
30. [30] May, P.C., Dean, R.A., Lowe, S.L., Martenyi, F., Sheehan, S.M., Boggs, L.N., et al. Robust central reduction of amyloid-beta in humans with an orally available, non-peptidic beta-secretase inhibitor. J Neurosci 31 (2011), 16507–16516.
31. [31] Willis, B., Martenyi, F., Dean, R., Lowe, S., Nakano, M., Monk, S., et al. Central BACE1 inhibition by LY2886721 produces opposing effects on APP processing as reflected by cerebrospinal fluid sAPPalpha and sAPPbeta. Alzheimers Dement, 8, 2012, P582.