Evidence map›Paper›PMID 38250767›Full record

ArticleJournal of Alzheimer's disease : JAD2024

Brain 11β-Hydroxysteroid Dehydrogenase Type 1 Occupancy by Xanamem™ Assessed by PET in Alzheimer's Disease and Cognitively Normal Individuals.

Victor L Villemagne, Vincent Doré, Lee Chong, Michael Kassiou, Rachel Mulligan, Azadeh Feizpour, Jack Taylor, Miriam Roesner, Tamara Miller, Christopher C Rowe

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Victor L VillemagneDepartment of Molecular Imaging and Therapy, Austin Health, Melbourne, VA, Australia.
Vincent DoréDepartment of Molecular Imaging and Therapy, Austin Health, Melbourne, VA, Australia.
Lee ChongDepartment of Molecular Imaging and Therapy, Austin Health, Melbourne, VA, Australia.
Michael KassiouThe University of Sydney, School of Chemistry, Sydney, Australia.
Rachel MulliganDepartment of Molecular Imaging and Therapy, Austin Health, Melbourne, VA, Australia.
Azadeh FeizpourDepartment of Molecular Imaging and Therapy, Austin Health, Melbourne, VA, Australia.
Jack TaylorActinogen Medical, Sydney, NSW, Australia.
Miriam RoesnerActinogen Medical, Sydney, NSW, Australia.
Tamara MillerActinogen Medical, Sydney, NSW, Australia.
Christopher C RoweDepartment of Molecular Imaging and Therapy, Austin Health, Melbourne, VA, Australia.
The University of Melbourne · AUAustin Health · AUCommonwealth Scientific and Industrial Research Organisation · AUThe University of Sydney · AUUniversity of Pittsburgh · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates intracellular cortisol and its inhibition by the small molecule inhibitor, Xanamem™, may provide a disease-modifying strategy for Alzheimer's disease (AD). Animal models suggest a range of 30-60% enzyme inhibition may suffice to provide neuroprotection.

objectiveTo determine the regional brain occupancy of 11β-HSD1 by Xanamem™ in cognitively normal participants (CN) and mild cognitive impairment (MCI)/mild AD patients to investigate potential dosing ranges for future efficacy studies.

methodsSeventeen MCI/AD and 23 CN were included. Regional brain time-activity curves (TAC), standardized uptake values (SUV40-60) and volume of distribution (VT) from Logan plot with image derived input function from 11C-TARACT positron emission tomography (PET) were used to assess the degree of 11β-HSD1 occupancy by increasing doses of Xanamem™ (5 mg, 10 mg, 20 mg or 30 mg daily for 7 days).

resultsAll measures showed high 11β-HSD1 occupancy with Xanamem to similar degree in CN and MCI/AD. The dose-response relationship was relatively flat above 5 mg. Respective median (interquartile range [Q1-Q3]) 11β-HSD1 occupancy in the MCI/AD and CN groups after treatment with 10 mg Xanamem were 80% [79-81%] and 75% [71-76%] in the neocortex, 69% [64-70%] and 61% [52-63%] in the medial temporal lobe, 80% [79-80%] and 73% [68-73%] in the basal ganglia, and 71% [67-75%] and 66% [62-68%] in the cerebellum.

conclusionsTAC, SUV40-60, and VT measures indicate Xanamem achieves high target occupancy levels with near saturation at 10 mg daily. These data support exploration of doses of≤10 mg daily in future clinical studies.

Indexed as

11-beta-Hydroxysteroid Dehydrogenase Type 1Alzheimer DiseaseThiophenesTropanesAnimalsBrainHumansPositron-Emission Tomography11-beta-Hydroxysteroid Dehydrogenase Type 1ThiophenesTropanesUE234311beta-hydroxysteroid dehydrogenase type 1Alzheimer’s diseasecortisoldrug developmentpositron emission tomographytarget occupancy

Identifiers

PMID38250767
PMCPMC10836555
OpenAlexW4391023474

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.