Laronidase
| Evidence Level: L4 | Predicted Indications: 2 |
Table of Contents
- Laronidase
- Laronidase: From Mucopolysaccharidosis Type I to Lysosomal Storage Disease with Skeletal Involvement
Laronidase: From Mucopolysaccharidosis Type I to Lysosomal Storage Disease with Skeletal Involvement
One-Sentence Summary
Laronidase (brand name Aldurazyme) is a recombinant alpha-L-iduronidase enzyme replacement therapy, originally used to treat mucopolysaccharidosis type I (MPS I). The TxGNN model predicts it may be effective for lysosomal storage disease with skeletal involvement, but this entry largely restates the drug’s known MPS I use rather than a true repurposing. Currently there are 0 clinical trials and 4 publications (reviews, an in vitro study and a case report) for this entry.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Mucopolysaccharidosis type I (MPS I). The license record has no indication text, so this comes from the literature. |
| Predicted New Indication | Lysosomal storage disease with skeletal involvement |
| TxGNN Prediction Score | 99.31% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 1 (BLA125058) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the record. Based on known information, laronidase is a recombinant form of the enzyme alpha-L-iduronidase. It replaces the deficient enzyme in MPS I (Hurler, Hurler-Scheie and Scheie syndromes).
When this enzyme is missing, glycosaminoglycans (dermatan sulfate and heparan sulfate) build up in tissues. In bone and cartilage this buildup causes skeletal disease (dysostosis multiplex). The predicted indication therefore sits directly downstream of the drug’s known target pathway. In vitro work shows laronidase is taken up by cultured fibroblasts and osteoblasts, mainly through mannose 6-phosphate receptors, and is transported to lysosomes.
This prediction is effectively the drug’s known MPS I use rather than a new repurposing. Skeletal endpoints in MPS I have shown only modest response, because intravenous enzyme cannot fully reach bone and cartilage. The Phase 3 RCT (PMID 15126990) supports MPS I but appears under the other predicted entry, not this one.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25345091 | 2014 | Review | Pediatr Endocrinol Rev | Overview of MPS I: alpha-L-iduronidase deficiency, its disease spectrum (Hurler, Hurler-Scheie, Scheie), and diagnosis by urinary glycosaminoglycans and enzyme assay |
| 12196045 | 2002 | Review | BioDrugs | Development overview of laronidase for MPS I, including US and European orphan drug designation and FDA fast-track status |
| 23127271 | 2012 | Case report | Pediatr Neurol | 6.5-year follow-up of a boy with attenuated MPS I (Scheie syndrome) on enzyme replacement therapy. His overall status declined and the disease progressed. |
| 18758061 | 2008 | Preclinical (in vitro) | Biol Pharm Bull | Laronidase was taken up by MPS I fibroblasts and osteoblasts dose-dependently, mainly via mannose 6-phosphate receptors, and reached lysosomes |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| BLA125058 | ALDURAZYME (Genzyme Corporation) | Injection, solution, concentrate | Not specified in the record |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The drug is already marketed in the US for MPS I, and the predicted indication overlaps with its known disease pathology. The evidence attached to this entry is only L4 (reviews, in vitro data and a case report). Skeletal response to intravenous enzyme has been modest.
To proceed, the following is needed:
- Package insert warnings and contraindications, which are missing and block safety screening
- Detailed mechanism of action data from DrugBank
- Skeletal-specific clinical endpoint data (for example, radiographic or joint range-of-motion outcomes) from controlled studies
- Confirmation of the FDA-approved indication text, which is missing from the license record
Related note: The second predicted indication, Sanfilippo syndrome (MPS III), is not supported. It involves different heparan sulfate-degrading enzymes that laronidase cannot replace, it is mainly neurological, and intravenous enzyme does not cross the blood-brain barrier effectively. No clinical trials were retrieved, and the retrieved literature is almost entirely about MPS I. Recommendation for that entry: Hold.
These results are for research reference only and do not constitute medical advice. Repurposing candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.