Rasagiline
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Rasagiline: From Parkinson Disease to PLA2G6-Associated Neurodegeneration
One-Sentence Summary
Rasagiline is a monoamine oxidase type B (MAO-B) inhibitor, originally used to treat Parkinson disease and related parkinsonian syndromes. The TxGNN model predicts it may be effective for PLA2G6-associated neurodegeneration (score 99.7%), but no clinical trials or publications currently support this specific prediction. The prediction rests on model output alone, so the evidence is weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Parkinson disease (and related parkinsonian syndromes) |
| Predicted New Indication | PLA2G6-associated neurodegeneration |
| TxGNN Prediction Score | 99.71% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on general knowledge, rasagiline is a selective, irreversible MAO-B inhibitor. It reduces dopamine breakdown in the brain, and its efficacy in Parkinson disease is established.
PLA2G6-associated neurodegeneration includes PARK14 dystonia-parkinsonism, so its clinical picture overlaps with parkinsonian phenotypes. This overlap probably explains the graph-based prediction. MAO-B inhibition could in principle ease dopaminergic symptoms. It would not be expected to change the underlying lipid-metabolism and iron-accumulation pathology. The link therefore remains speculative.
Other predicted indications worth noting (all from the same model run):
- Lewy body dementia (score 98.8%, Evidence Level L4): biologically plausible because it shares alpha-synuclein pathology with Parkinson disease. The supporting literature is mostly preclinical, review-type, or about adjacent conditions such as Alzheimer's disease. A Phase II trial in mild to moderate Alzheimer's disease (PMID 33614888) is indirect evidence only. No trial in Lewy body dementia itself was identified. This is the most evidence-supported prediction, and it is framed as a research question.
- Retinal dystrophy (score 98.8%, Evidence Level L4): a single mouse study in retinitis pigmentosa (PMID 29372592) reported delayed retinal degeneration. No human data were found.
- Paralysis agitans, juvenile, of Hunt (score 99.2%): a juvenile parkinsonism syndrome very close to the approved indication. The high score probably reflects ontology proximity rather than independent evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for PLA2G6-associated neurodegeneration.
For the related Lewy body dementia prediction, the most relevant publications are:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33614888 | 2021 | Phase II RCT (Alzheimer's, indirect) | Alzheimer's & Dementia (N Y) | Tested rasagiline 1 mg daily for 24 weeks versus placebo on brain glucose metabolism, cognition and tau in mild to moderate Alzheimer's disease |
| 36232361 | 2022 | Review | Int J Mol Sci | Neuroprotective function of rasagiline and selegiline, and the role of MAO in synucleinopathies |
| 38412454 | 2024 | Preclinical / drug design | Arch Pharm | Neflamapimod-rasagiline hybrid compounds designed for Lewy body dementia |
| 29769405 | 2018 | Preclinical mechanistic | EMBO J | Alpha-synuclein binds and stimulates MAO-B, which drives Parkinson disease pathology |
| 20555137 | 2010 | Preclinical | J Alzheimers Dis | Propargylamine compounds, including rasagiline, modulate amyloid precursor protein processing |
| 38988416 | 2024 | Biomarker study (Alzheimer's, indirect) | Alzheimer's & Dementia (N Y) | Relationships among plasma biomarkers, tau PET, FDG PET and MRI in the rasagiline Phase 2 trial population |
| 17197368 | 2006 | Review | Neurotox Res | Multifunctional neuroprotective drugs such as ladostigil, which combines rasagiline's pharmacophore with cholinesterase inhibition |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15291P | AZILECT TABLET 1MG (Teva Pharmaceutical Industries, Ltd.) | Tablet | Not stated in the data compiled for this report |
Safety Considerations
- Contraindications (from knowledge-graph associations, not label text): hypertensive disorder, hypertension, multiple system atrophy, postural orthostatic tachycardia syndrome, orthostatic hypotension, drug-induced dyskinesia, epilepsy, bipolar disorder, major affective disorder, liver disease, gallbladder disease, melanoma, pheochromocytoma and other adrenal or paraganglionic tumours (including sympathetic paraganglioma), duodenum cancer, small intestine cancer, heart cancer, adrenal gland cancer. These need verification against the official package insert.
- Drug Interactions: the interaction screen returned 100 records. The main ones are:
- Major: bupropion, morphine
- Moderate: epinephrine, cimetidine, phentermine, diethylpropion, dronabinol, diphenoxylate, difenoxin, obeticholic acid, chlorpropamide, glimepiride, and multiple insulins (aspart, degludec, detemir, glargine, glulisine, human isophane, human regular, inhaled rapid-acting)
The HSA package insert warnings and contraindications were not available. Please refer to the package insert for the full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The PLA2G6-associated neurodegeneration prediction is supported only by the model score, with no trials or publications. MAO-B inhibition is not expected to affect the underlying disease pathology. Among the other predictions, Lewy body dementia and retinal dystrophy are the more plausible research questions. Both have only indirect, preclinical or adjacent-disease evidence (Level L4).
To proceed, the following is needed:
- The HSA package insert warnings and contraindications (currently a blocking gap for safety screening)
- Detailed mechanism of action data from DrugBank
- Disease-specific preclinical or clinical evidence for PLA2G6-associated neurodegeneration, if this indication is pursued
- For Lewy body dementia: a dedicated trial or pilot study addressing cognitive and neuropsychiatric endpoints and tolerability
- For retinal dystrophy: replication in additional animal models and an assessment of ocular exposure and safety
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.