Cycloserine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Cycloserine: From Tuberculosis to Irritable Bowel Syndrome
One-Sentence Summary
Cycloserine is a second-line antibiotic used mainly for multidrug-resistant tuberculosis (MDR-TB). The TxGNN model predicts it may be effective for Irritable Bowel Syndrome, with a very high prediction score of 99.95%, but currently no clinical trials and no published literature support this specific link — the prediction is model-driven only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Tuberculosis, particularly multidrug-resistant TB (based on evidence-pack rationale text; no formal UK licence data available — see below) |
| Predicted New Indication | Irritable Bowel Syndrome |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L5 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism-of-action data is not available in the regulatory registry for this drug (flagged as a High-severity data gap). Based on information available elsewhere in the evidence pack, cycloserine is a second-line anti-tuberculosis antibiotic that inhibits bacterial cell-wall synthesis (D-alanine racemase/ligase inhibition), and its D-isomer also acts centrally as an NMDA receptor glycine-site partial agonist.
Its efficacy in MDR-TB is well established. However, no mechanistic or clinical connection between this profile and irritable bowel syndrome — a gut-brain axis / visceral hypersensitivity disorder — has been identified in the trials or literature reviewed. The evidence pack’s own rationale explicitly flags this: the TxGNN score is extremely high (99.95%) yet is entirely unsupported by trial or publication evidence, and should be treated as a potential knowledge-graph artefact rather than a genuine pharmacological signal. The same pattern (very high score, zero supporting evidence, no mechanistic rationale) recurs across most of the other top-10 predictions for this drug (acne, gastroparesis, conjunctivitis, pharyngitis, nasal cavity disease, acute laryngopharyngitis, postgastrectomy syndrome, rhinitis), suggesting a possible model clustering bias around antimicrobial/mucosal-disease nodes that warrants separate methodological review.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
UK Market Information
Cycloserine currently holds no UK marketing authorisations (market status: not marketed, total licences: 0). No dosage form or product information is available for the UK market.
Safety Considerations
No structured warnings, contraindications, or interaction data are currently available in the registry for cycloserine (flagged as a Blocking-severity data gap — TFDA/SmPC label data has not yet been obtained). Please refer to the SmPC and BNF for safety information once available. Report suspected adverse reactions via the Yellow Card Scheme.
Note: literature identified during evidence review for a separate, unrelated candidate indication (insomnia) describes cycloserine-induced insomnia and psychosis in a patient treated for MDR-TB (PMID 36712725), consistent with cycloserine’s known CNS/neuropsychiatric adverse effect profile (dose-related seizures, psychosis, confusion, sleep disturbance). This should be considered when evaluating any centrally active repurposing candidate for this drug.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction (irritable bowel syndrome) has an Evidence Level of L5 — a high TxGNN score with no supporting clinical trials or literature — and no plausible mechanistic link has been established. Cycloserine is also not currently marketed in the UK, and critical safety data (SmPC warnings/contraindications, confirmed MOA) remain outstanding, which blocks even a preliminary safety assessment.
To proceed, the following is needed:
- TFDA/SmPC warning and contraindication data (currently a Blocking gap)
- Confirmed mechanism-of-action data via DrugBank (currently a High-severity gap)
- Dedicated mechanistic or preclinical studies linking cycloserine to gut-brain axis pathophysiology, since none currently exist
- A methodological review of whether the cluster of unsupported high-scoring predictions (IBS, acne, gastroparesis, and the ENT/mucosal-disease group) reflects a genuine signal or a knowledge-graph co-occurrence artefact
- If pursuing repurposing in the UK at all, a new marketing authorisation pathway, since the drug is not currently licensed here
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.