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Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer's disease: results of a randomized, double-blind, placebo-controlled phase 2a study
Scheltens P, Hallikainen M, Grimmer T, Duning T, Gouw AA, Teunissen CE, Wink AM, Maruff P et al.. Alzheimer's research & therapy, 2018-10-12
Topic: Amyloid, tau and blood-test diagnosis
Results There was no significant difference between treatments in the number of subjects with (serious) adverse events, although there were slightly more patients with a serious adverse event in the PQ912 group compared to placebo. PQ912 treatment resulted in a significant reduction in glutaminyl cyclase activity, which resulted in an average target occupancy of > 90%. A significant reduction of theta power in the EEG frequency analysis and a significant improvement in the One Back test of our Neuropsychological Test Battery was observed. Conclusions The maximal tolerated dose of PQ912 has been identified and the results support future studies at still lower doses reaching > 50% target occupancy, a longer up-titration phase to potentially induce adaptation and longer treatment periods to confirm the early signals of efficacy as seen in this study.
Key findings
- Results There was no significant difference between treatments in the number of subjects with (serious) adverse events, although there were slightly more patients with a serious adverse event in the PQ912 group compared to placebo.
- PQ912 treatment resulted in a significant reduction in glutaminyl cyclase activity, which resulted in an average target occupancy of > 90%.
- A significant reduction of theta power in the EEG frequency analysis and a significant improvement in the One Back test of our Neuropsychological Test Battery was observed.
- Conclusions The maximal tolerated dose of PQ912 has been identified and the results support future studies at still lower doses reaching > 50% target occupancy, a longer up-titration phase to potentially induce adaptation and longer treatment periods to confirm the early signals of efficacy as seen in this study.
Why it matters
In a phase 2a trial in people with Alzheimer's, the glutaminyl cyclase inhibitor PQ912 cut the target enzyme's activity, reaching an average target occupancy of > 90%, and was linked to a reduction in EEG theta power and better scores on one memory test. Serious adverse events were slightly more common than on placebo, though not significantly different. The authors see only early signals of efficacy and call for longer studies at lower doses.
Study details
- Study designrandomized controlled trial
- Evidence strengthHigh
How this study scored 66/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 127 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.7 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 6.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 2 / 4 | Cited 46 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Niels D. Prins: h-index 54 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | King's College London: institution h-index 1,348 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30309389) |
| Free to read | 2 / 2 | Free to read |
| Total | 66 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13195-018-0431-6
- PubMed: 30309389
- Original source →
- Free full text: Alzheimer s Research & Therapy →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Scheltens, P., Hallikainen, M., Grimmer, T., Duning, T., Gouw, A. A., Teunissen, C. E., et al. (2018). Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer's disease: results of a randomized, double-blind, placebo-controlled phase 2a study. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-018-0431-6
Vancouver
Scheltens P, Hallikainen M, Grimmer T, Duning T, Gouw AA, Teunissen CE, et al. Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer's disease: results of a randomized, double-blind, placebo-controlled phase 2a study. Alzheimer's research & therapy. 2018. doi:10.1186/s13195-018-0431-6. PMID: 30309389.
BibTeX
@article{scheltens2018-30309389,
author = {Scheltens, P. and Hallikainen, M. and Grimmer, T. and Duning, T. and Gouw, A. A. and Teunissen, C. E. and Wink, A. M. and Maruff, P. and others},
title = {{Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer's disease: results of a randomized, double-blind, placebo-controlled phase 2a study}},
journal = {Alzheimer's research \& therapy},
year = {2018},
doi = {10.1186/s13195-018-0431-6},
pmid = {30309389},
url = {https://doi.org/10.1186/s13195-018-0431-6}
}
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