O4‐06‐07: Imaging and cerebrospinal fluid biomarker results of a phase II dose‐ranging study of ELND005 (Scyllo‐inositol) in mild‐to‐moderate Alzheimer's disease
Bibliographic record
Abstract
ELND005 (scyllo-inositol) is being investigated as a potential disease modifying oral agent for the treatment of Alzheimer's disease (AD). ELND005 inhibits aggregation of beta-amyloid (Abeta) and decreases plaque burden intransgenic TgCRND8 mice (McLaurin et al., 2006). In addition to clinical outcomes, this study investigated the effects of ELND005 on volumetric MRI measures (vMRI) and cerebrospinal fluid (CSF) biomarkers. Of 353 mild/moderate patients randomized to ELND005 (250, 1000, or 2000mg) or placebo twice daily for 78weeks, 351 received study drug. Brain ventricular volume (VV) was designated as the key imaging biomarker; exploratory endpoints included whole brain volume, average hippocampal volume, and cortical ribbon thickness. MRIs were performed in all patients at baseline and every 24 weeks. CSF samples from a subset of patients at baseline, 24 weeks, and 78 weeks were tested for Aß40, Aß42, tau, and p-tau181 levels. All primary anaylses were performed using a mixed-effects model repeated measures analysis. After elective discontinuation of the 2 high-dose groups due to safety findings, the primary analysis compared the 250mg and placebo groups. In the overall population, the VV increase at week 78 was greater for ELND005 than placebo (VV increase of 3.2cm;p = 0.049; n = 84/82 in 250mg/placebo), while other brain volume measures were not significant. In mild patients, who showed a positive trend on this study's primary cognitive endpoint (Salloway et al, submitted), the VV increase of 0.3cm was not significant. In mild/moderate patients, CSF biomarker changes were not significant at 24 weeks, but CSF Aß42 was significantly decreased at 78 weeks (p = 0.009, n = 19/14 in 250 mg/placebo), other CSF biomarker changes were not significant. Patients treated with ELND005 250mg demonstrated a significant decrease in CSF Aß42 levels and a small, but significant,increase in ventricular volume after 78 weeks of treatment. Similar MRI findings have been reported in clinical trials with other amyloid-targeted therapies. The time course of CSF Aß42 reduction may reflect a gradual decrease in brain amyloid pathology, consistent with the effects of scyllo-inositol in transgenic mice.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".