Didanosine

證據等級: L5

預測適應症: 3 個

Drug: Didanosine (NRTI antiretroviral; MOA is [Data Gap] but inferred from literature context in the pack)
Top prediction: Feline AIDS — a veterinary, non-human disease; unusual scope for NL human healthcare
NL market: No CBG-MEB authorizations (0 licenses, not marketed)
Safety data: All [Data Gap] → omit, refer to SmPC
Not antineoplastic → omit Cytotoxicity section
Evidence: L4 (animal/in vitro studies only, 0 clinical trials)

Didanosine: From HIV Infection to Feline Acquired Immunodeficiency Syndrome

One-Sentence Summary

Didanosine (ddI) is a nucleoside reverse transcriptase inhibitor (NRTI) established for the treatment of HIV infection in humans. The TxGNN model predicts it may be effective for Feline Acquired Immunodeficiency Syndrome (caused by feline immunodeficiency virus, FIV), with 0 clinical trials and 3 publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	HIV infection (antiretroviral therapy; NRTI class)
Predicted New Indication	Feline Acquired Immunodeficiency Syndrome
TxGNN Prediction Score	99.33%
Evidence Level	L4
NL Market Status	Not marketed in the Netherlands
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this Evidence Pack. Based on known information, Didanosine is a dideoxynucleoside-class NRTI whose active metabolite — dideoxyadenosine triphosphate (ddATP) — competitively inhibits viral reverse transcriptase and terminates elongating proviral DNA. Its efficacy against HIV, a retroviral lentivirus, is well established after decades of clinical use.

Feline acquired immunodeficiency syndrome is caused by feline immunodeficiency virus (FIV), which belongs to the same lentivirus family as HIV. Both viruses depend on a reverse transcriptase enzyme for replication. This shared biological architecture is why the TxGNN model assigns a high similarity score: in principle, ddATP could inhibit FIV reverse transcriptase by the same chain-termination mechanism. PMID 17616550 explicitly uses a FIV-infected cat model to study didanosine’s effects, confirming the drug does reach and act within this biological system.

However, two critical caveats must be stated clearly. First, FIV reverse transcriptase differs from HIV-1 RT in substrate-binding residues, so cross-activity is not guaranteed and requires dedicated experimental validation. Second — and more fundamentally — feline acquired immunodeficiency syndrome is a veterinary disease affecting cats, not humans. This places the top-ranked TxGNN prediction outside the standard scope of human drug repurposing for the Netherlands healthcare system. The evidence base is limited to animal and in vitro studies, with no registered clinical trials in any population.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
17616550	2007	Animal toxicity study	Brain	Didanosine induces sensory neuropathy in FIV-infected cats (ex vivo and in vivo ATN model); impaired mitochondrial and neurotrophic factor gene expression. Demonstrates ddI pharmacological activity in FIV-infected hosts, though in a toxic rather than therapeutic context.
2540111	1989	Animal experiment	Intervirology	FeLV (feline leukaemia virus)-infected cats used as an antiretroviral chemotherapy model; ddI (2’,3’-dideoxyinosine) tested in vitro against feline retroviral replication alongside AZT and other dideoxynucleosides — earliest evidence of ddI activity in feline retroviral systems.
19380511	2009	Animal neuroscience study	FASEB Journal	CXCR3-mediated neuronal injury during lentiviral infection studied in FIV/HIV models; antiretroviral therapy (including ddI-class agents) shown to have neuroprotective effects, supporting mechanistic overlap between FIV and HIV treatment pathways.

Netherlands Market Information

Didanosine currently holds no marketing authorizations with CBG-MEB (College ter Beoordeling van Geneesmiddelen). It is not registered or marketed in the Netherlands. No RVG numbers are on record.

Safety Considerations

Please refer to the SmPC (Summary of Product Characteristics) for safety information. Full SmPC data for Didanosine can be accessed via the EMA product registry or the originating regulatory authority’s database.

Note: SmPC retrieval is flagged as a blocking data gap (DG001) for this Evidence Pack. The CBG-MEB/TFDA label, including warnings and contraindications, must be obtained and reviewed before any repurposing decision can progress past the initial screening stage.

Conclusion and Next Steps

Decision: Hold

Rationale: The highest-ranked TxGNN prediction for Didanosine is a veterinary disease (feline acquired immunodeficiency syndrome in cats), which falls outside the scope of human drug repurposing for the Dutch healthcare system. All available supporting evidence consists of animal and in vitro studies (Evidence Level L4), no clinical trials are registered in any registry, and Didanosine holds zero CBG-MEB authorizations in the Netherlands.

To proceed, the following is needed:

Scope clarification: Confirm whether veterinary indications are within the programme’s remit; if not, re-rank to focus on the second-ranked human-relevant prediction (Simian Immunodeficiency Virus infection, L3, 12 publications)
SmPC retrieval (DG001 — Blocking): Obtain the full label from EMA or originating authority to complete the S1 safety screening; this is a prerequisite for any further evaluation
MOA data (DG002 — High): Query DrugBank API to formally confirm the NRTI mechanism and enable structured mechanistic analysis
FIV-specific pharmacology: If veterinary application is explored, conduct dedicated in vitro susceptibility testing of FIV reverse transcriptase against ddATP to determine cross-species activity
Regulatory pathway assessment: If redirected toward the SIV indication or another human indication, evaluate whether existing EMA/ICH guidelines cover a new repurposing application, and identify whether an off-label use framework or a new MAA is more appropriate for the Netherlands context
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.