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@ARTICLE{Kutzsche:1043479,
      author       = {Kutzsche, Janine and Cosma, Nicoleta Carmen and Kauselmann,
                      Gunther and Fenski, Friederike and Bieniek, Christine and
                      Bujnicki, Tuyen and Pils, Marlene and Bannach, Oliver and
                      Willbold, Dieter and Peters, Oliver},
      title        = {{O}ral {PRI}-002 treatment in patients with {MCI} or mild
                      {AD}: a randomized, double-blind phase 1b trial},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {FZJ-2025-02882},
      pages        = {4180},
      year         = {2025},
      abstract     = {Self-replicating amyloid beta (Aβ) oligomers are
                      considered as one of the major drivers for disrupted
                      synaptic function and plasticity, leading to impaired
                      neuronal viability and progression of Alzheimer’s disease
                      (AD). Here, we investigated the safety, tolerability and
                      pharmacokinetics of the anti-oligomeric peptide PRI-002,
                      which was developed to disassemble toxic Aβ oligomers into
                      non-toxic monomers. In a randomized, double-blind,
                      single-center phase 1b trial, 20 patients aged between 50
                      and 80 years, with mild neurocognitive impairment (MCI) or
                      mild dementia due to AD were recruited. Eligible patients
                      were randomly assigned (1:1) to receive 300 mg PRI-002
                      once daily (q.d.) or placebo for 28 days. During treatment,
                      study visits were performed on baseline (Day 1), Day 14, Day
                      28 and an additional follow-up visit on Day 56. Safety
                      assessments were carried out at all visits to determine the
                      primary endpoints. On Day 7 and Day 21 additional phone
                      visits were carried out to assess concomitant meds and AEs.
                      Primary endpoints were nature, frequency, severity, and
                      timing of adverse and serious adverse events (AE/SAEs) and
                      treatment discontinuation. Furthermore, standard laboratory
                      values, electrocardiogram (ECG), electroencephalogram (EEG),
                      magnetic resonance imaging (MRI), and vital signs were
                      assessed. Secondary endpoints included the evaluation of
                      pharmacokinetic characteristics of PRI-002 in plasma and the
                      determination of cerebrospinal fluid (CSF) concentrations of
                      PRI-002. The trial is registered in EudraCT 2020-003416-27
                      and clinicaltrials.gov NCT04711486. In the study, 19 out of
                      20 patients were randomly assigned to PRI-002 (n = 9) or
                      placebo (n = 10) and completed the study. One patient
                      withdrew informed consent before randomization. All primary
                      endpoints were met. Overall, the study drug was well
                      tolerated. In total n = 16 AEs were reported in the
                      verum group, while n = 27 AEs were noted in the placebo
                      group. No SAEs were reported. No significant changes in
                      clinical chemistry, hematology or hematoserology were
                      detected. ECG, EEG and MRI revealed no changes and in detail
                      no ARIA were observed. Pharmacokinetic parameters were
                      unrelated to sex, age, and weight. Furthermore, no
                      significant changes were detected in p-tau, t-tau, Aβ 1-40,
                      Aβ 1-42 and Aβ oligomers in CSF. Patients receiving
                      PRI-002 performed significantly better than those receiving
                      placebo in the CERAD word list at Day 56 (P ≤ 0.05).
                      In conclusion, 28 days of treatment with 300 mg q.d.
                      PRI-002 was well tolerated in patients with MCI or mild
                      dementia due to AD.},
      cin          = {IBI-7},
      ddc          = {500},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5244},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {40324978},
      UT           = {WOS:001482771100001},
      doi          = {10.1038/s41467-025-59295-z},
      url          = {https://juser.fz-juelich.de/record/1043479},
}