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The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease

Neumann, Ulf and Ufer, Mike and Jacobson, Laura and Rouzade-Dominguez, Marie-Laure and Huledal, Gunilla and Kolly, Carine and Lueoend, Rainer Martin and Machauer, Rainer and Veenstra, Siem and Hurth, Konstanze and Shimshek, Derya and Staufenbiel, Matthias and Perrot, Ludovic and Frieauff, Wilfried and Dubost, Valerie and Schiller, Hilmar and Vogg, Barbara and Beltz, Karen and Avrameas, Alexandre and Kretz, Sandrine and Pezous, Nicole and Rondeau, Jean-Michel and Beckmann, Nicolau and Hartmann, Andreas and David, Olivier and Galli, Bruno and Ramos, Rita and Graf, Ana and Lopez Lopez, Cristina and Vormfelde, Stefan (2018) The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease. EMBO molecular medicine, 10 (11). S227-S228. ISSN 17574684

Abstract

The beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) initiates the generation of amyloid-β (Aβ), and the amyloid cascade leading to amyloid plaque deposition, neurodegeneration, and dementia in Alzheimer's disease (AD). Clinical failures of anti-Aβ therapies in dementia stages suggest that treatment has to start in the early, asymptomatic disease states. The BACE-1 inhibitor CNP520 has a selectivity, pharmacodynamics, and distribution profile suitable for AD prevention studies. CNP520 reduced brain and cerebrospinal fluid (CSF) Aβ in rats and dogs, and Aβ plaque deposition in APP-transgenic mice. Animal toxicology studies of CNP520 demonstrated sufficient safety margins, with no signs of hair depigmentation, retina degeneration, liver toxicity, or cardiovascular effects. In healthy adults ≥ 60 years old, treatment with CNP520 was safe and well tolerated and resulted in robust and dose-dependent Aβ reduction in the cerebrospinal fluid. Thus, long-term, pivotal studies with CNP520 have been initiated in the Generation Program.

Item Type: Article
Keywords: Alzheimer's disease BACE‐1 inhibitor drug discovery prevention β‐amyloid
Date Deposited: 03 Jan 2019 00:45
Last Modified: 03 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/34356

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