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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},
}