P1‐067: Pilot Study of Sublimed Sulfur Targeting Hydrogen Sulfide (H<sub>2</sub>S) and Beta‐Galactosidase (GALAC) in Hyper‐Homocyteinemia (EHCT) and Alzheimer’S Disease (AD): Opportunities for Novel Therapeutic Avenue in AD
Bibliographic record
Abstract
Recent evidence suggests that hyper-homocysteinemia(eHct) correlates with cognitive decline severity and cortical atrophy in AD. Hydrogen Sulfide (H2S) exerts neuroprotection through regulating Homocysteine (Hct) signaling and neurovascular coupling. Elemental sulfur, in converting to H2S, mediates H2S neuroprotection through the trans-sulfuration pathway. Sublimed Sulfur, formulated as SULMEDOL and approved for the treatment of lactose intolerance, activates beta-galactosidase (GALAC). Dysregulation of the expression of senescence-related GALAC in the brain results in impaired endosomal-lysosomal autophagy system in AD. We hypothesize that sublimed Sulfur (SS), via targeting H2S/Hct and GALAC, may be efficacious in eHcT and in modifying cognitive decline in AD. We examined: 1) whether SS can reset plasma homocysteine level in patients with hyper-homocysteinemia (eHct) ; 2) whether SS is safe and efficacious in improving AD symptoms. In study I we recruited 46 subjects with significant cardio-vascular history who were stratified into: Group I: fasting-Hct (fHct) >9·9 μmol/L, Group 2: 7·1 to 9·9 μmol/L, Group 3: fHct <7·1 μmol/L. The 3 groups received 30-day oral SS 200 mg daily. Primary outcome consisted of fHct normalization. In study II, two AD patients were treated with SS 200 mg for 3 months, with Clinical Global Impression–Global Improvement (CGI –I) scale as the primary outcome measure. In Study I, Group I subjects, fHct decreased significantly by 36·1%, 24 hours after treatment (t15, 0·05 = –3·9, p = 0·0014), and by 29·3%, 30 days later (t15, 0·05 = -3·80, p= 0·0018). In Group 2 fHct did not change significantly. Group 3 exhibited paradoxical non-significant increase in fHcy,without change in erythrocyte folic acid, serum lipids and vitamin B12. SS was well tolerated in eHct patients. In Study II, clinical vignette analysis of the two community-dwelling AD patients revealed that 3-month SS treatment ameliorated cluster of AD symptoms: nocturnal wandering, paranoid delusions, disorientation and confusion. CGI-I scale score was 1=“very much improved”. None of the subjects reported serious adverse events. SS holds promise as a potential therapeutic agent in AD in resetting hyper-homocysteinemia, and dual targeting H2S-homocysteine inflammation signaling and GALAC autophagy pathway related to AD. Our findings warrant controlled trial of SS in AD.
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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 | 0.001 | 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) | 0.004 | 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".