Progesterone, trigeminal nerve targets, and dry eye disease
This report evaluates progesterone (drug), trigeminal pathway gene proxies (TRPV1, TRPM8, SCN9A, CHRM3), and dry eye disease (indication) using the Open Targets Platform. Dry eye is represented by ontology proxies (e.g. Sjögren syndrome); trigeminal-mediated biology by gene-level proxies. All data are query-backed; framing is designed for strategic and R&D interpretation.
This report is for strategic and due-diligence use only; it does not constitute regulatory, medical, or investment advice.
For methodology, see How it’s built.
Data: Open Targets Platform. Interpretation: Biotica Bio.
Progesterone in the Platform
Biology that matters: Progesterone acts via nuclear hormone receptor signalling. Sex hormones influence meibomian gland lipid production and lacrimal gland function; clinical literature supports hormonal modulation of dry eye, especially in post-menopausal populations. Progesterone is not a “dry eye drug” in the Platform, but it sits in a hormonal modulation axis of tear film physiology—a bridge to neuro-lacrimal and gland-modulation hypotheses.
Platform profile: Progesterone is a Small molecule. Small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 1976 and has 3 approved and 44 investigational indications. This drug has a black box warning from the FDA.
Mechanism and targets (Platform):
| Target | Mechanism |
|---|---|
| Progesterone receptor | Progesterone receptor agonist |
Indications (top 7 of 47 in Platform):
| Indication |
|---|
| anorexia nervosa |
| Osteopenia |
| cervical intraepithelial neoplasia |
| breast carcinoma |
| hemorrhage |
| Vulvar Lichen Sclerosus |
| bulimia nervosa |
Dry eye / ocular: No indication in the Platform explicitly matches dry eye or ocular-related terms; the biological link is literature-supported hormonal effects on tear physiology, not a direct Open Targets indication.
Dry eye disease (Open Targets)
Framing: Dry eye is poorly represented as a single node in ontologies; it is often split across keratoconjunctivitis sicca, Sjögren syndrome, and ocular surface disease. We use ontology proxies that overlap clinically with dry eye. Open Targets is strongest for autoimmune drivers (e.g. Sjögren) and weaker for multifactorial symptom syndromes—that nuance is a valuable insight, not a limitation.
Proxies in this report: EFO_0000699. (Sjögren syndrome)
| Disease | EFO ID | Therapeutic area(s) |
|---|---|---|
| Sjogren syndrome | EFO_0000699 | immune system disease; gastrointestinal disease; disorder of visual system |
Known drugs (Platform, this node): 85 total. Top 10:
| Drug | Phase | Target |
|---|---|---|
| PILOCARPINE | 4 | CHRM1 |
| PILOCARPINE | 4 | CHRM3 |
| ABATACEPT | 3 | CD80 |
| HYDROXYCHLOROQUINE | 3 | TLR7 |
| HYDROXYCHLOROQUINE | 3 | TLR9 |
| DEUCRAVACITINIB | 3 | TYK2 |
| DAZODALIBEP | 3 | CD40LG |
| IANALUMAB | 3 | TNFRSF13C |
| IANALUMAB | 3 | TNFRSF13C |
| ABATACEPT | 3 | CD86 |
Associated targets (Platform): 2748 total. Top 10:
| Target | Score |
|---|---|
| IRF5 | 0.490 |
| STAT4 | 0.424 |
| GTF2I | 0.387 |
| CHRM3 | 0.374 |
| ATG2B | 0.372 |
| CHRM1 | 0.370 |
| TNFRSF13C | 0.367 |
| TRMU | 0.362 |
| COX7B2 | 0.358 |
| RBFOX1 | 0.355 |
Open Targets is a tool for target identification and prioritisation; it may not fully enumerate the commercial dry eye market.
Trigeminal nerve–related targets
Framing: The trigeminal nerve is an anatomical structure; Open Targets indexes genes, not nerves. We represent trigeminal-mediated biology (ocular sensation, reflex tear secretion, sensory transmission) by gene-level proxies: TRPV1 (nociception/inflammation), TRPM8 (cold/tear reflex), SCN9A (Nav1.7, sensory transmission), CHRM3 (lacrimal parasympathetic). Open Targets will not return “trigeminal nerve” but returns these components of trigeminal signalling biology.
Targets in this report: TRPV1, TRPM8, SCN9A
TRPV1
transient receptor potential cation channel subfamily V member 1 (ENSG00000196689).
Pathways: Transport of small molecules
Known drugs: 343. Top: CAPSAICIN, ACETAMINOPHEN, ACETAMINOPHEN, ACETAMINOPHEN, CAPSAICIN
Associated diseases: 853 total; top: migraine disorder, Pain, Headache, Fever, common cold, Back pain, pharyngitis, arthritis
TRPM8
transient receptor potential cation channel subfamily M member 8 (ENSG00000144481).
Pathways: Transport of small molecules
Known drugs: 46. Top: MENTHOL, MENTHOL, MENTHOL, MENTHOL, MENTHOL
Associated diseases: 308 total; top: Pain, Cough, Back pain, arthritis, pharyngitis, common cold, sprain, Pruritus
SCN9A
sodium voltage-gated channel alpha subunit 9 (ENSG00000169432).
Pathways: Sensory Perception; Muscle contraction; Developmental Biology
Known drugs: 988. Top: DRONEDARONE HYDROCHLORIDE, PROPAFENONE HYDROCHLORIDE, ZONISAMIDE, ZONISAMIDE, PRIMIDONE
Associated diseases: 541 total; top: primary erythermalgia, paroxysmal extreme pain disorder, channelopathy-associated congenital insensitivity to pain, autosomal recessive, hereditary sensory and autonomic neuropathy type 2, epilepsy, Channelopathy-associated congenital insensitivity to pain, Seizure, hereditary sensory and autonomic neuropathy
Integration
Progesterone ↔ dry eye: No direct Open Targets linkage in this dataset; literature-supported hormonal effects on tear physiology suggest indirect relevance (hormonal modulation axis).
Trigeminal pathway ↔ dry eye: Component targets (e.g. TRPV1, TRPM8, CHRM3) connect sensory signalling to tear production. CHRM3 appears in the dry eye–associated target set (concrete link between neuro/lacrimal signalling and this indication). Overlap with dry eye–associated targets: yes.
Synthesis: Open Targets emphasises immune/inflammatory biology (e.g. Sjögren targets such as IRF5, STAT4). The progesterone/trigeminal hypothesis emphasises neuro-reflex and hormonal modulation of lacrimal/meibomian function. These are orthogonal mechanistic spaces, not overlapping ones—that contrast is the signal.
Commercial take: The dry eye market is crowded (anti-inflammatory, tear stabilisation). The emerging niche is neurostimulation / endogenous tear activation (e.g. Tyrvaya). Progesterone is not a direct competitor but supports a biological plausibility layer (gland modulation). Pro-ocular-style positioning is not “another dry eye drug” but a neuro-lacrimal activation strategy, adjacent to but distinct from immune modulation and lubrication.
R&D take: Open Targets is useful here not for confirming the mechanism, but for showing what it is not: the dominant target landscape in the Platform is immune signalling; the proposed mechanism is neural reflex activation. That contrast is the insight.
Data provenance
Report generated from the Open Targets Platform GraphQL API. Entity resolution uses an ontology translation table (config/ontology-translation.json): dry eye → EFO proxies (EFO_0000699; Sjögren syndrome), trigeminal pathway → gene proxies (TRPV1, TRPM8, SCN9A, CHRM3). Queries: drug (CHEMBL103), disease (dry eye EFO IDs), target-summary (Ensembl IDs: ENSG00000196689, ENSG00000144481, ENSG00000169432). Re-run: node fetch-progesterone-trigeminal-dry-eye.js then node generate-progesterone-trigeminal-dry-eye-report.js (optional --from-json and --out).
Data: Open Targets Platform. Interpretation: Biotica Bio.