Histidine
| Evidence Level: L5 | Predicted Indications: 2 |
Table of Contents
Histidine: From Maple Syrup Urine Disease to Gastroparesis
One-Sentence Summary
Histidine (marketed as Maapliv) was originally authorized in the EU for acute decompensation episodes of maple syrup urine disease (MSUD). The TxGNN model predicts it may be effective for gastroparesis, but this rests on model output alone: 0 clinical trials and 1 publication were found, and that publication does not test histidine.
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 and enteral branched-chain amino acids free (BCAA-free) formulation |
| Predicted New Indication | Gastroparesis |
| TxGNN Prediction Score | 99.55% |
| Evidence Level | L5 |
| EU Market Status | Cancelled only (no currently valid authorization) |
| Number of Authorizations | 1 (cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Histidine is an amino acid, and its authorized use in MSUD is as part of parenteral amino acid nutrition during acute metabolic decompensation. That use is nutritional and metabolic, and it has no direct connection to gastric motility.
Any link to gastroparesis is speculative. One possible route is histidine’s role as the precursor of histamine, which can influence gastric secretion and motility. No study retrieved for this report tests this idea. The only publication found concerns gastric amyloid pathology and mucosal denervation in hereditary ATTR amyloidosis, and it does not involve histidine or treatment of gastroparesis.
The very high TxGNN score (rank 5664) reflects a pattern in the knowledge graph, not confirmed biological or clinical support.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42668409 | 2026 | Preclinical/clinical pathology study | Amyloid | Describes gastric amyloid pathology and mucosal denervation in hereditary ATTR amyloidosis (patients and mice). Does not test histidine and does not address gastroparesis treatment. |
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-chai… |
Safety Considerations
- Disease associations from the knowledge graph (not label text): The TxGNN knowledge graph lists contraindication links between histidine and several conditions. These are kidney disease (including chronic kidney disease, chronic renal failure and end-stage renal failure), nephrolithiasis and nephrocalcinosis, hypercalcemia-related conditions (including humoral hypercalcemia of malignancy and sarcoidosis), phosphorus metabolism disease, heart and cardiovascular disease, ventricular fibrillation, digitalis poisoning, acute urate nephropathy, pyoureter, and phenylketonuria or other disorders of phenylalanine metabolism. These links come from a computational graph, not from product labelling, and need verification.
Please refer to the SmPC for authoritative safety information, including warnings, contraindications and drug interactions. No drug interaction records were found.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, but there is no clinical trial, no direct preclinical study, and no mechanistic data linking histidine to gastroparesis. The only retrieved publication is unrelated to histidine therapy. The EU authorization is also cancelled, so the drug has no active EU marketing status.
To proceed, the following is needed:
- Mechanism of action data for histidine, and a plausible mechanistic hypothesis for gastric motility
- Preclinical studies of histidine or histamine-pathway modulation in gastroparesis models
- The SmPC warnings and contraindications, to complete safety screening
- Clarification of the knowledge-graph contraindication signals, especially renal and cardiovascular conditions, which are common in patients with gastroparesis
- Confirmation of why the EU authorization was cancelled, and of its regulatory implications
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.