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@ARTICLE{Willbold:863338,
author = {Willbold, Dieter and Kutzsche, Janine},
title = {{D}o {W}e {N}eed {A}nti-{P}rion {C}ompounds to {T}reat
{A}lzheimer’s {D}isease?},
journal = {Molecules},
volume = {24},
number = {12},
issn = {1420-3049},
address = {Basel},
publisher = {MDPI75390},
reportid = {FZJ-2019-03418},
pages = {2237 -},
year = {2019},
abstract = {While phase III clinical trials for the treatment of
Alzheimer’s disease (AD) keep failing regardless of the
target, more and more data suggest that the toxic protein
assemblies of amyloid-beta protein (Aβ) and tubulin binding
protein (TAU) behave like prions. Irrespective of the
question of whether AD is theoretically or practically
contagious, the presence of a self-replicating toxic
etiologic agent in the brains of AD patients must have
decisive consequences for drug development programs and
clinical trial designs. Objectives: We intend to challenge
the hypothesis that the underlying etiologic agent of AD is
behaving prion-like. We want to discuss whether the outcome
of clinical trials could have been predicted based on this
hypothesis, and whether compounds that directly disassemble
the toxic prion could be more beneficial for AD treatment.
Method: We collected publicly accessible pre-clinical
efficacy data of Aβ targeting compounds that failed or
still are in phase III clinical trials. We describe the
desired properties of an anti-prion compound and compare it
the properties of past and current phase III drug
candidates. Results: We could not find convincing and
reproducible pre-clinical efficacy data of past and current
phase III drug candidates on cognition other than in
preventive treatment settings. The desired properties of an
anti-Aβ-prionic compound are fulfilled by the drug
candidate RD2, which has been developed to directly
disassemble toxic Aβ oligomers. Conclusion: RD2 is the
first anti-prion drug candidate. It is able to enhance
cognition and impede neurodegeneration in three different
transgenic AD mouse models, even under truly non-preventive
conditions and even when applied orally. In addition, it is
safe in humans.},
cin = {ICS-6},
ddc = {540},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31208037},
UT = {WOS:000473816900043},
doi = {10.3390/molecules24122237},
url = {https://juser.fz-juelich.de/record/863338},
}