Riluzole
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Riluzole
- Riluzole: From Amyotrophic Lateral Sclerosis to Bilateral Parasagittal Parieto-Occipital Polymicrogyria
Riluzole: From Amyotrophic Lateral Sclerosis to Bilateral Parasagittal Parieto-Occipital Polymicrogyria
One-Sentence Summary
Riluzole is an oral medicine originally used to treat amyotrophic lateral sclerosis (ALS). The TxGNN model predicts it may be effective for bilateral parasagittal parieto-occipital polymicrogyria, but no clinical trials and no publications currently support this prediction. The top prediction rests on a model score alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Amyotrophic lateral sclerosis (the Singapore licence record contains no indication text; this comes from the TxGNN knowledge graph) |
| Predicted New Indication | Bilateral parasagittal parieto-occipital polymicrogyria |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available for this report. Based on known information, riluzole is understood to dampen glutamate signalling and limit excitotoxic injury to motor neurons. That is the likely basis of its benefit in ALS.
Polymicrogyria is a malformation of cortical development, often accompanied by epilepsy. Altered glutamate signalling could plausibly play a role, but this link is speculative. The data compiled for this report contain no study connecting riluzole to this condition. The high score may partly reflect patterns in the knowledge graph rather than a real biological relationship.
Other predictions in the top 10 (all prediction-only unless noted):
- Motor neuron disorders are mechanistically close to ALS, so they are the most plausible by analogy. These are lower motor neuron syndrome with late-adult onset, monomelic amyotrophy, Mills syndrome, and ALS type 22. All are rated "Research Question".
- ALS, susceptibility to is a genetic label for the original indication, not a true new use. It has the only supporting literature in the dataset.
- Weak or no mechanistic rationale: axial spondylometaphyseal dysplasia, trichomegaly-retina pigmentary degeneration-dwarfism syndrome, lethal arthrogryposis-anterior horn cell disease syndrome, and autosomal dominant mitochondrial myopathy with exercise intolerance. All are rated "Hold".
The ALS type 22 entry appears misspelled in the source ("amyotrohpic"), which may have limited literature retrieval. A repeat search with the corrected spelling is advisable.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
No literature was found for the top-ranked prediction (polymicrogyria). The table below shows the only literature in the dataset, which relates to rank 8, "ALS, susceptibility to", essentially the original indication. It is shown for context only and is not evidence for a new use. Of 20 publications supplied, 10 are listed.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42161327 | 2026 | Cohort | Brain | CYP2D6 variants studied for association with ALS risk and survival. Riluzole's survival benefit is modest and likely varies between patients. |
| 9178165 | 1997 | Review | Journal of Neurology | Glutamate excitotoxicity as a major mechanism of motor neuron injury in ALS. |
| 21128691 | 2011 | Review | CNS Drugs | ALS pathophysiology and management. Riluzole is the one medication shown to modestly prolong survival. |
| 16723044 | 2006 | Review | Expert Reviews in Molecular Medicine | Proposed ALS mechanisms (oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation) and routes to treatment. |
| 20698807 | 2011 | Review | Amyotrophic Lateral Sclerosis | Riluzole, thought to affect glutamate metabolism, improves survival modestly. Disease heterogeneity and trial design may explain negative trials. |
| 31108504 | 2019 | Preclinical | Human Molecular Genetics | Altered calcium dynamics and glutamate receptor properties in iPSC-derived motor neurons from ALS patients. |
| 8061281 | 1994 | Preclinical | Neuroreport | Riluzole showed neuroprotective effects against ALS cerebrospinal fluid toxicity in neuronal cultures. |
| 32040174 | 2020 | Modelling study | Toxicological Sciences | Liver-function modelling of a sublingual riluzole formulation versus the 50 mg tablet. About 50% of ALS patients on oral riluzole have ALT above the upper limit of normal. |
| 20942785 | 2010 | Review | CNS & Neurological Disorders Drug Targets | Genetic determinants of ALS as therapeutic targets. Riluzole extends survival by only 2–3 months. |
| 41280004 | 2025 | Preprint | bioRxiv | Riluzole studied as a radiosensitizer for osteosarcoma. Not related to the predicted indications. |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09426P | RILUTEK TABLET 50 mg | Film-coated tablet (oral) | Indication text not recorded in the licence data |
Manufacturer: Opella Healthcare International SAS.
Safety Considerations
Package insert warnings and contraindications could not be retrieved for this report. Please refer to the package insert for safety information.
Contraindication-related conditions from the knowledge graph (not label text, so they need confirmation against the package insert):
- Neutropenia and agranulocytosis
- Substance abuse/dependence
- Hyperbilirubinemia, hereditary hyperbilirubinemia, and Gilbert syndrome
- Interstitial lung disease
- Drug-induced liver injury
Published data also show raised liver enzymes (ALT) in about half of ALS patients taking oral riluzole, so liver monitoring is relevant (PMID 32040174).
Drug interactions: 44 interactions were identified. The main ones are listed below.
- Moderate: obeticholic acid, naltrexone, deferasirox, osilodrostat, anagrelide, asparaginase Escherichia coli, brentuximab vedotin, clofarabine, methotrexate, epirubicin
- Minor: omeprazole, caffeine, theophylline, aminophylline
- Severity unclassified: metformin, simvastatin, ranitidine, cyanocobalamin, salbutamol, ibuprofen
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction has only a model score (99.99%), with no trials, no literature and no clear mechanistic rationale. The evidence level is L5. The data-quality issues, including missing package insert safety data, also prevent safety screening.
To proceed, the following is needed:
- Package insert warnings and contraindications for the Singapore product
- Detailed mechanism of action data
- A targeted literature and trial search for polymicrogyria and for the motor neuron disorders (monomelic amyotrophy, Mills syndrome, lower motor neuron syndrome, ALS type 22), using corrected disease spellings
- Review of the motor neuron predictions as the most plausible research questions, while recognising that ALS-related entries largely duplicate the original indication
- A hepatic and haematological safety monitoring plan, given the liver and neutropenia signals
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.