Alanine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Alanine: From Maple Syrup Urine Disease (Acute Decompensation) to Gastroparesis
One-Sentence Summary
Alanine (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 no clinical trials and only 3 indirectly related publications are available, so this prediction rests on computation alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | 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 | 99.37% |
| 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. Alanine is a non-essential amino acid that takes part in the glucose-alanine cycle and gluconeogenesis. Its authorized use in MSUD is as part of parenteral amino acid nutrition during metabolic crisis.
No credible mechanistic link between alanine and gastric motility has been established. The very high prediction score (0.994) is a purely computational output. Without known pharmacology to cross-check it, any connection to gastroparesis remains speculative.
The three retrieved publications cover gastrointestinal and hepatic complications of kidney disease, diabetic hepatosclerosis, and glycogen hepatopathy in type 1 diabetes. They mention gastroparesis only as a comorbidity or background context. None of them tests alanine as a treatment.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 10926110 | 2000 | Review | Advances in Renal Replacement Therapy | Gastrointestinal and liver disorders in end-stage renal disease and transplant recipients; gastroparesis is more common in chronic renal failure. Alanine is not studied. |
| 26315331 | 2016 | Review | Diabetic Medicine | Diabetic hepatosclerosis as a possible microvascular complication of diabetes. Not related to alanine treatment. |
| 33763324 | 2021 | Case report/Review | Cureus | Glycogen hepatopathy in a type 1 diabetic patient whose history included gastroparesis. Gastroparesis appears only as a comorbidity. |
EU Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| EMEA/H/C/005557 (cancelled) | Maapliv | Not specified | Maple syrup urine disease (MSUD) presenting with an acute decompensation episode in patients from birth who are not eligible for an oral and… |
Safety Considerations
Disease associations in the knowledge graph (not label text) suggest possible contraindications or cautions in these areas:
- Kidney disease: chronic kidney disease, chronic renal failure, end-stage renal failure, nephrolithiasis, nephrocalcinosis, acute urate nephropathy
- Cardiovascular disease: heart disease, digitalis poisoning, ventricular fibrillation
- Calcium and phosphorus disorders: hypercalcemia, humoral hypercalcemia of malignancy, sarcoidosis, phosphorus metabolism disease
- Amino acid metabolism disorders: phenylketonuria and other disorders of phenylalanine metabolism
No drug interaction records were found. Please refer to the SmPC for label-based warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported only by the TxGNN score (L5). There are no clinical trials, no mechanistic rationale, and the retrieved literature does not address alanine for gastroparesis. The only EU authorization has been cancelled, so there is no currently marketed product to build on.
To proceed, the following is needed:
- Mechanism of action data to assess any plausible link to gastric motility
- Targeted literature searches for alanine or amino acid therapy in gastroparesis, plus preclinical studies if none exist
- The SmPC warnings and contraindications, which are needed before any safety screening
- Review of the knowledge-graph contraindications, especially renal and cardiac conditions, since gastroparesis patients often have diabetes and kidney disease
- Clarification of route and formulation, since the original product was parenteral and its suitability for gastroparesis is unknown
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.