Ursodeoxycholic Acid
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Ursodeoxycholic Acid: Homozygous familial hypercholesterolemia
One-Sentence Summary
Ursodeoxycholic acid (UDCA) was originally used to treat gallstone disease (cholelithiasis, cholecystolithiasis and choledocholithiasis), primary biliary cholangitis and Reynolds syndrome. The TxGNN model predicts it may be effective for homozygous familial hypercholesterolaemia, but there are currently 0 clinical trials and 0 publications supporting this prediction. It is a model prediction only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Homozygous familial hypercholesterolemia |
| TxGNN Prediction Score | 0.9986 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, UDCA is a bile acid that affects bile acid and cholesterol handling, including reduced intestinal cholesterol absorption and modulation of hepatic cholesterol secretion. These effects are the basis of its use in gallstone disease and cholestatic liver disease.
This gives a loose link between the original indications and a lipid disorder. However, homozygous familial hypercholesterolaemia is defined by deficient LDL receptor function. UDCA’s modest effects on cholesterol handling are unlikely to compensate for that defect, so the mechanistic link is speculative.
The high TxGNN score reflects a computational association only. The other top-ranked predictions are mostly rare genetic conditions (for example COL4A1-related small vessel disease and platelet disorders) with the same lack of supporting evidence.
Clinical Trial Evidence
Currently no related clinical trials registered for homozygous familial hypercholesterolaemia.
Literature Evidence
Currently no related literature available for homozygous familial hypercholesterolaemia.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42857346 | 2026 | Clinical study (proof-of-concept; design to be verified) | Front Endocrinol | Effect of UDCA on albuminuria in people with type 1 diabetes and diabetic kidney disease; results not available in the data compiled |
| 27193377 | 2016 | Preclinical | Biol Pharm Bull | UDCA, an ER stress inhibitor, reduced oxidative stress and improved diabetic nephropathy in db/db mice |
| 26999661 | 2016 | Preclinical | Lab Invest | UDCA and 4-phenylbutyrate prevented ER stress-induced podocyte apoptosis in db/db mice |
| 22429686 | 2012 | Preclinical | Diabetes Res Clin Pract | UDCA decreased SGLT2 expression and oxidative stress in the kidneys of diabetic rats |
| 18648192 | 2008 | Preclinical (in vitro) | Am J Nephrol | Taurine-conjugated UDCA reduced ER stress and apoptosis in cultured mouse podocytes |
| 39384774 | 2024 | Observational | Nutr Diabetes | Bile acid metabolism is altered step-wise in patients with diabetic kidney disease |
| 23977286 | 2013 | Preclinical | PLoS One | ER stress is involved in albuminuria-induced inflammasome activation in renal tubular cells (indirect evidence) |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 11180K | Ursofalk | Tablet 500 mg (oral) | Not available in the data compiled |
Safety Considerations
- Drug Interactions: The interaction screen returned 100 potential interactions, of which only a sample was available for this report. Minor interactions listed were with cyclosporine, aluminium hydroxide and magaldrate. Many others (for example pravastatin, ramipril, lorazepam, tramadol, fluconazole, erythromycin, sildenafil, pantoprazole, citalopram, moxifloxacin, nelfinavir, glimepiride and indinavir) have an unclassified severity level and need individual review.
For warnings and contraindications, please refer to the TGA-approved Product Information (PI).
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction for homozygous familial hypercholesterolaemia rests on a model score alone (L5), with no trials or publications. The proposed mechanism is unlikely to offset the underlying LDL receptor deficiency.
To proceed, the following is needed:
- Any clinical or mechanistic evidence of UDCA effects on LDL cholesterol in LDL receptor-deficient patients
- Detailed mechanism of action data
- TGA Product Information warnings and contraindications for Ursofalk, and the approved indication text
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.