Threonine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Threonine: From Maple Syrup Urine Disease (Acute Decompensation) to Gastroparesis
One-Sentence Summary
Threonine is an amino acid, formulated as Maapliv, and was originally authorised in the EU for acute decompensation episodes of maple syrup urine disease (MSUD). The TxGNN model predicts it may be useful for gastroparesis, but no clinical trials and no publications currently support this direction, so it rests on a computational prediction alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Treatment of maple syrup urine disease (MSUD) presenting with an acute decompensation episode in patients from birth who are not eligible for an oral or enteral BCAA-free formulation |
| Predicted New Indication | Gastroparesis |
| TxGNN Prediction Score | 99.32% |
| Evidence Level | L5 |
| EU Market Status | Cancelled only (no currently valid authorisation) |
| Number of Authorizations | 1 (cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, threonine is an essential amino acid. Its approved use in MSUD is as part of a parenteral amino acid supply for patients who cannot take oral or enteral BCAA-free formulations. That is a metabolic and nutritional indication, not a gastrointestinal one.
A possible but unverified link is that threonine is a precursor of glycine and serine and a major component of intestinal mucins. In theory this could relate to gut mucosal integrity or to neurotransmitter pathways involved in gastric motility. Nothing in the data compiled for this report confirms a role in gastroparesis, so this link is speculative.
The original and predicted indications are mechanistically distant: one is an inborn error of branched-chain amino acid metabolism, the other a disorder of delayed gastric emptying. The high TxGNN score (99.32%) is a knowledge-graph computation and should not be read as clinical evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
EU Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| EMEA/H/C/005557 (cancelled) | Maapliv | Not specified | Maapliv is indicated for the treatment of maple syrup urine disease (MSUD) presenting with an acute decompensation episode in patients from birth who are not eligible for an oral and enteral branched-chain amino acids free (BCAA- free) formulation. |
Safety Considerations
- Knowledge-graph contraindication signals: The TxGNN knowledge graph (PrimeKG) links threonine with contraindications in phenylketonuria and disorders of phenylalanine metabolism. These come from graph relationships, not from label text, and should be verified against the SmPC.
Please refer to the SmPC for the remaining safety information, including warnings and drug interactions. No interaction records were found for this drug.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a model score. There are no clinical trials, no literature, and no mechanism data linking threonine to gastroparesis. The only EU authorisation is cancelled, and the label safety information has not been reviewed.
To proceed, the following is needed:
- Label warnings and contraindications from the EMA documentation, which is needed before any safety screening
- Mechanism of action data for threonine, and a plausible mechanistic rationale for gastric motility
- A literature search and a trial registry search for threonine or amino acid supplementation in gastroparesis or related motility disorders
- Verification of the knowledge-graph contraindications (phenylketonuria, phenylalanine metabolism disorders)
- An assessment of route and formulation compatibility, since the approved product is for acute use and the route required for gastroparesis is undetermined
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.