Altering neuronal circuitry with 4-aminopyridine for visual improvement in Leber’s hereditary optic neuropathy (LHON)
Bibliographic record
Abstract
In this retrospective, interventional, longitudinal small case series, we looked at the visual effects of pharmacologic intervention with 4-aminopyridine (4-AP) in chronic Leber's Hereditary Optic Neuropathy (LHON) patients who are non-responders to idebenone. We illustrate, as examples, the visual progression of three LHON patients with 4-AP as add-on therapy to idebenone. Each patient had a different primary LHON mutation and was treated with idebenone within one year of onset. No response to idebenone at 300 mg orally three times a day ranged from less than one year to 2.5 years, and the addition of 4-AP at 10 mg orally two times a day ranged from 24 to 29 months. Outcome measures included best-corrected distance visual acuity, color vision, automated perimetry, the average retinal nerve fiber layer (RNFL) thickness, and the full-field photopic negative response (PhNR) amplitude. The 19-year-old man with the LHON mutation 11778A > G had no response to the addition of 4-AP to idebenone. The 27-year-old man with the LHON mutation 3460A > G experienced a significant response to 4-AP. Finally, the 40-year-old man with the LHON mutation 14484 T > C had a milder response. Although this case series was too small to demonstrate the efficacy of idebenone with add-on 4AP, it allowed us to consider a new hypothesis that neuronal activity generated from 4-AP can add more potential for visual recovery in LHON patients.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".