Nasal administration of Protollin enhances monocyte phagocytosis and decreases CD8+ T cell cytotoxicity in subjects with early Alzheimer’s disease: A phase 1 clinical trial
Bibliographic record
Abstract
ABSTRACT Protollin, a nasal adjuvant, was evaluated in a randomized double-blind phase 1 study of 16 early Alzheimer’s disease (AD) patients to determine safety and to assess its immunomodulatory effects. In a double-blind dose escalation study, subjects received nasal Protollin at doses of 0.1mg, 0.5mg, 1.0mg, and 1.5mg or placebo twice over a two-week period. Treatment was well-tolerated with minimal side effects. Transcriptomic and single-cell analyses demonstrated that prior to treatment, AD blood monocytes had downregulation of phagocytosis-related genes and an increased pro-inflammatory signature. These AD monocyte abnormalities were reversed by nasal Protollin beginning at a dose of 1.0mg. Protollin induced a robust phagocytic gene signature, including upregulation of CD36 , ITGAL , LYST , and FCGR1A . A similar phagocytic signature was observed in brain- infiltrating amyloid-clearing monocytes in an APP Tg mouse model treated with nasal Protollin. Protollin treatment decreased the expression of costimulatory molecules on monocytes and decreased CD8+ T cell activation and cytotoxicity. Our results provide the basis for a phase 2 study of nasal Protollin in subjects with AD in which nasal Protollin at a dose of 1.0 mg will be administered weekly over 6 months to modulate peripheral immunity and clear amyloid from the brain. ClinicalTrials.gov registration no NCT07187141 .
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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 | 0.000 |
| 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 | 0.000 |
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".