Lactic Acid

證據等級: L5

預測適應症: 10 個

Lactic Acid: From No Registered Indication to Multiple TxGNN‑Predicted Candidates (Screening Review)

One-Sentence Summary

Lactic acid (DrugBank DB04398) has no approved indication on record in this evidence pack and is not currently marketed in Australia. TxGNN generated ten candidate new indications, but on evidence review the top-ranked candidates (structural cardiovascular and congenital malformations) appear to be artefacts of knowledge-graph keyword co-occurrence rather than genuine mechanistic signals, while two lower-ranked candidates — dry eye syndrome/Sjögren’s syndrome and eye disease more broadly — are supported by real (but directionally inconsistent) mechanistic literature on lactate metabolism in ocular tissue.

Quick Overview

Item	Content
Original Indication	Not available — no approved indication on record for this product
Predicted New Indication (TxGNN top rank)	Atypical coarctation of aorta
TxGNN Prediction Score (top rank)	99.59%
Evidence Level (top rank)	L5
Best-Supported Alternative Candidates	Dry eye syndrome (L3) / Eye disease (L3)
Australia Market Status	Not marketed
Number of ARTG Entries	0
Recommended Decision	Hold

Screening Summary — All Predicted Indications Reviewed

Because this evidence pack evaluates a panel of ten TxGNN candidates rather than a single indication, the table below summarises the full screening outcome before drilling into detail.

Rank	Predicted Indication	TxGNN Score	Evidence Level	Decision Stage	Recommendation
1	Atypical coarctation of aorta	99.59%	L5	S0	Hold
2	Aortic malformation	99.35%	L4	S0	Hold
3	Non-syndromic esophageal malformation	99.23%	L5	S0	Hold
4	Amenorrhea (disease)	99.16%	L4	S0	Hold
5	Dry eye syndrome	99.13%	L3	S1	Research Question
6	Esophageal disease	98.94%	L5	S0	Hold
7	Double outlet right ventricle with AVSD, pulmonary stenosis, heterotaxy	98.82%	L5	S0	Hold
8	Excretory apparatus of the lacrimal system anomaly	98.77%	L5	S0	Hold
9	Eye disease	98.68%	L3	S1	Research Question
10	Cauda equina syndrome	98.67%	L5	S0	Hold

Key observation: the top five TxGNN scores are clustered within a narrow band (99.59%–99.13%), yet evidence quality diverges sharply. Ranks 1, 3, 7, 8 and 10 are congenital/structural anatomical conditions requiring surgical correction, with zero clinical trials or literature retrieved — these are not diseases a small organic acid can plausibly treat. Ranks 2, 4 and 6 returned trial/literature hits, but manual review found these to be keyword coincidences (e.g., “aorta”, “esophageal”) unrelated to lactic acid pharmacology. Only ranks 5 and 9 (both eye/ocular-surface conditions) returned literature with a genuine, biologically active role for lactate in the relevant tissue.

Why is This Prediction Reasonable?

Detailed mechanism of action data for lactic acid is not available in this evidence pack (original_moa: [Data Gap]), and no original approved indication is recorded, so the usual “original indication → new indication” mechanistic bridge cannot be constructed here. Lactic acid is the terminal product of glycolysis and a systemic/tissue pH-modulating metabolite; it does not have a defined pharmacological mechanism for reversing anatomical malformations, which explains why ranks 1, 3, 6, 7, 8 and 10 (all structural/congenital conditions) are assessed as prediction noise — TxGNN’s knowledge graph appears to have linked lactic acid to these diseases through indirect metabolic/cardiovascular node co-occurrence rather than a causal treatment relationship.

The more scientifically interesting signal sits with dry eye syndrome (rank 5) and eye disease (rank 9). Multiple mechanistic studies show lactate and its post-translational modification “lactylation” are biologically active in ocular tissues — in the lacrimal glands (Sjögren’s syndrome), sclera (myopia), and choroid/retina (neovascularisation, diabetic retinopathy). However, in essentially all of these studies lactate acts as a pathological/pro-inflammatory driver, not a therapeutic agent: it promotes cGAS-STING inflammatory signalling in Sjögren’s acinar cells, drives histone lactylation that accelerates scleral remodelling in myopia, and upregulates VEGF to promote choroidal neovascularisation. This is the opposite direction to what a “repurposing for treatment” hypothesis requires, so while the biology is real, it does not currently support using lactic acid therapeutically for these conditions — it flags a research question, not a treatment opportunity.

No clinical trial in this pack administers lactic acid as an investigational treatment for any of the ten predicted indications; all clinical trial hits are coincidental keyword matches (e.g., perioperative lactate monitoring, unrelated drugs tested in cardiac/ocular populations).

Clinical Trial Evidence

Currently no clinical trials registered that test lactic acid as a treatment for any of the ten predicted indications. All retrieved trials (across ranks 2, 4, 5, 6 and 9) were manually graded and found to be coincidental keyword matches — studies of unrelated drugs, surgical techniques, or devices in patient populations that happen to share disease-name keywords with the predicted indication (e.g., “aorta,” “esophageal,” “eye”). No ANZCTR identifiers were present in the source data.

Representative examples of why trials were excluded as irrelevant:

Trial Number	Phase	Status	Enrolment	Why Excluded
NCT01920594	Phase 2	Completed	57	Tests GSK1278863 (HIF-PH inhibitor) for aortic aneurysm repair — no pharmacological link to lactic acid
NCT03237312	Phase 2	Completed	50	PCOS ovarian drilling study; amenorrhoea keyword match only
NCT03544281	Phase 1/2	Completed	153	Antibody-drug conjugate for multiple myeloma; matched to “dry eye” only via unrelated adverse-event terminology
NCT01791595	Phase 1	Completed	53	Tests AZD3965 (a monocarboxylate transporter/lactate-transport inhibitor) in advanced cancer — mechanistically the inverse of lactic acid administration
NCT02511613	Phase 2	Withdrawn	0	Tests squalamine lactate (an unrelated aminosterol salt), not lactic acid itself, for macular degeneration

Literature Evidence

No literature directly tests lactic acid as a therapeutic agent for any predicted indication. The table below lists the most relevant mechanistic literature — concentrated on ranks 5 and 9 — describing lactate/lactylation biology in ocular and lacrimal tissue. This evidence explains why the disease nodes are connected to lactic acid in the knowledge graph, but points toward lactate as a disease driver rather than a treatment.

PMID	Year	Type	Journal	Key Findings
39054226	2025	Review	Trends in Molecular Medicine	Reviews lactate/lactylation signalling in eye morphogenesis and disease, including myopia, intraocular malignancy, and retinal angiogenesis
37786436	2023	Basic/Mechanistic	International Journal of Medical Sciences	Lactate-induced mitochondrial DNA accumulation activates cGAS-STING signalling and inflammation in Sjögren’s syndrome (a major cause of dry eye)
40759752	2025	Basic/Mechanistic	Nature Metabolism	Lactate signalling aggregates immune-inflammatory hotspots in autoimmune tissue; SLC5A12 (lactate transporter) blockade resolves them
38232735	2024	Basic/Mechanistic	Cell Metabolism	Increased scleral glycolysis/lactate promotes myopia via histone lactylation in animal models
30046816	2018	Basic/Mechanistic	Investigative Ophthalmology & Visual Science	Lactic acid upregulates VEGF in macrophages and facilitates choroidal neovascularisation
34251320	2021	Metabolomics/Cohort	Clinical and Experimental Rheumatology	Serum metabolomics identifies disturbed lactate-related pathways as potential biomarkers in Sjögren’s syndrome
31491425	2019	Cohort/Biochemical	Experimental Eye Research	Vitreous pH and lactic acid concentration are elevated in patients with diabetes mellitus
3367436	1988	Cohort/Mechanistic	Journal of Vascular Surgery	Aortic wall lactate/glycolytic metabolism differs proximal/distal to experimental coarctation — an indirect metabolic association only, not treatment evidence

Australia Market Information

Lactic acid has no ARTG (Australian Register of Therapeutic Goods) entries in this evidence pack (total_licenses: 0) and its market status is recorded as not marketed in Australia. No product/brand, dosage form, or approved indication text is available to summarise.

Safety Considerations

Safety data for this product is currently a blocking data gap: TGA/TFDA-equivalent product label warnings and contraindications were not available (key_warnings and contraindications both return “[Data Gap]”), and a drug interaction (DDI) query returned no results. This gap is flagged in the evidence pack as Blocking severity, meaning it prevents the candidate from proceeding to an initial safety assessment (S1) regardless of predicted-indication evidence strength.

Please refer to the TGA-approved Product Information (PI) for safety information once a marketed formulation and label are identified.

Conclusion and Next Steps

Decision: Hold

Rationale: No predicted indication in this pack reaches a level of evidence that would justify progressing past initial screening. The TxGNN top-ranked candidates are structural/congenital conditions with no plausible drug-treatable mechanism and no supporting trials or literature — most likely knowledge-graph noise. The two candidates with genuine mechanistic literature (dry eye syndrome, eye disease) point to lactate as a disease-promoting, not therapeutic, metabolite, which runs counter to the repurposing hypothesis. Separately, a Blocking data gap (missing TFDA/TGA-equivalent product warnings) means this candidate cannot yet undergo a basic safety evaluation even if a promising indication were identified.

To proceed, the following is needed:

TFDA/TGA product label (warnings, contraindications) — currently a Blocking gap preventing any S1 safety assessment
Confirmed mechanism of action (MOA) data from DrugBank or another primary source
Clarification of the original approved indication(s), if any, for this specific product/formulation
If pursuing the dry eye/ocular research question further: preclinical or clinical evidence testing lactate modulation (e.g., lactate transporter inhibition) as a treatment strategy, rather than relying on evidence that characterises lactate as a pathological driver
Re-run of TxGNN screening interpretation with disease-node specificity checks, given the apparent keyword-coincidence pattern seen across 6 of the 10 candidates
Disclaimer

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