Open AccessThe BACE ‐1 inhibitor CNP 520 for prevention trials in Alzheimer's disease
Author(s) -
Neumann Ulf,
Ufer Mike,
Jacobson Laura H,
RouzadeDominguez MarieLaure,
Huledal Gunilla,
Kolly Carine,
Lüönd Rainer M,
Machauer Rainer,
Veenstra Siem J,
Hurth Konstanze,
Rueeger Heinrich,
TintelnotBlomley Marina,
Staufenbiel Matthias,
Shimshek Derya R,
Perrot Ludovic,
Frieauff Wilfried,
Dubost Valerie,
Schiller Hilmar,
Vogg Barbara,
Beltz Karen,
Avrameas Alexandre,
Kretz Sandrine,
Pezous Nicole,
Rondeau JeanMichel,
Beckmann Nicolau,
Hartmann Andreas,
Vormfelde Stefan,
David Olivier J,
Galli Bruno,
Ramos Rita,
Graf Ana,
Lopez Lopez Cristina
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809316
Subject(s) - library science , medicine , computer science
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 CNP 520 has a selectivity, pharmacodynamics, and distribution profile suitable for AD prevention studies. CNP 520 reduced brain and cerebrospinal fluid ( CSF ) Aβ in rats and dogs, and Aβ plaque deposition in APP ‐transgenic mice. Animal toxicology studies of CNP 520 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 CNP 520 was safe and well tolerated and resulted in robust and dose‐dependent Aβ reduction in the cerebrospinal fluid. Thus, long‐term, pivotal studies with CNP 520 have been initiated in the Generation Program.