Mefolinate (5‐methyltetrahydrofolate), but not folic acid, decreases mortality in an animal model of severe methylenetetrahydrofolate reductase deficiency
Bibliographic record
Abstract
Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) results in homocystinuria, with a variety of neurological and vascular complications, and sometimes death in the first year of life. MTHFR (EC 1.5.1.20) catalyses the synthesis of 5-methyltetrahydrofolate (5-methylTHF) which is required for homocysteine remethylation to methionine. Mthfr (-/-) mice are a good animal model of severe MTHFR deficiency in humans. They have marked hyperhomocysteinaemia and a high rate of mortality in the neonatal period. We attempted to rescue Mthfr (-/-) mice from postnatal death by treating their Mthfr (+/-) mothers with mefolinate (a synthetic form of 5-methylTHF, dissolved in their drinking water) or with a folic acid-enriched diet throughout pregnancy and lactation. We monitored pups' vitality and body weights until 3 weeks of age. The majority of Mthfr (-/-) pups from the control groups died during the first week of life. Body weights of -/- pups from control groups were significantly less than those of their Mthfr (+/-) and Mthfr ( +/+ ) littermates. Mefolinate treatment significantly improved survival rates (64% survival) in the -/- pups and improved morphology of the cerebellum. Folic acid supplementation did not affect the survival rate or body weights of the -/- pups. Our study suggests that MTHFR is important for postnatal growth and vitality, and that 5-methylTHF deficiency contributes to the high postnatal mortality. Mefolinate may be a good candidate drug for treatment of severe MTHFR deficiency.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".