VP Disease Emergence Kit — catalytic output (v0.32.0)
The VP Disease Emergence Kit reads 72 single-gene diseases as switch perturbations and forces each corrective DIRECTION. For the 10 diseases with no approved therapy, it surfaces 4 cross-disease repurposing hypotheses from same-axis approved donors and reports 6 honest orphan directions. Every claim is direction-only, graded [O]: no dose, efficacy, or individual medical advice.
Cross-disease repurposing hypotheses
4 cross-disease repurposing hypotheses are surfaced: for each no-approved disease below, an agent CLASS already approved for a disease sharing the same (axis-family, direction, lever) is proposed as a testable corrective-DIRECTION hypothesis — mechanism class only, never dose or efficacy.
| Recipient (no approved agent) | Shared axis-family | Direction / lever | Donor (approved agent class) | Novelty |
|---|---|---|---|---|
| choroideremia | retinal_gene_replacement | UP / replace | leber_congenital_amaurosis_2 (subretinal AAV gene replacement) | low-novelty (confirmatory: the recipient already pursues this mechanism class -- the scanner here merely VALIDATES its same-axis logic, a sanity check) |
| x_linked_retinitis_pigmentosa | retinal_gene_replacement | UP / replace | leber_congenital_amaurosis_2 (subretinal AAV gene replacement) | low-novelty (confirmatory: the recipient already pursues this mechanism class -- the scanner here merely VALIDATES its same-axis logic, a sanity check) |
| huntington_disease | toxic_gof_protein | UP / reduce | sod1_amyotrophic_lateral_sclerosis (SOD1-lowering antisense oligonucleotide); transthyretin_amyloidosis (TTR-lowering siRNA / antisense) | low-novelty (confirmatory: the recipient already pursues this mechanism class -- the scanner here merely VALIDATES its same-axis logic, a sanity check) |
| rho_autosomal_dominant_retinitis_pigmentosa | toxic_gof_protein | UP / reduce | sod1_amyotrophic_lateral_sclerosis (SOD1-lowering antisense oligonucleotide); transthyretin_amyloidosis (TTR-lowering siRNA / antisense) | low-novelty (confirmatory: the recipient already pursues this mechanism class -- the scanner here merely VALIDATES its same-axis logic, a sanity check) |
Caveat (forced): same-axis ≠ same-disease. Each row is a mechanism-CLASS direction hypothesis, not a prediction; donor and recipient differ in tissue, delivery, allele, and off-target biology, any of which may defeat repurposing. No magnitude is claimed [O].
Open-directions cards (no-approved tail)
10 open-directions cards render the no-approved tail as actionable: 4 carry a concrete candidate drug class from a same-axis approved donor and 6 are honest orphan directions. Each card gives the single CHEAPEST experiment that would refute the forced direction.
| Disease | Forced direction / lever (status) | Candidate drug class (← approved-for donor) | Cheapest falsification experiment |
|---|---|---|---|
| choroideremia | UP / replace (clinical) | subretinal AAV gene replacement ← leber_congenital_amaurosis_2 | ERG, OCT outer-nuclear-layer / autofluorescence area and microperimetry response to AAV2-REP1 in REP1-deficient retina (mouse, patient) |
| dravet_syndrome | UP / replace (investigational) | — (orphan: no same-axis approved donor) | seizure frequency on SCN1A upregulation vs on a sodium-channel blocker in Scn1a+/- mice / Dravet patients (the phenytoin / carbamazepine worsening is the predicted control) |
| hereditary_haemorrhagic_telangiectasia | DOWN / restrain (clinical) | — (orphan: no same-axis approved donor) | arteriovenous-malformation burden / endothelial-activation markers in response to ALK1/endoglin-pathway restoration in HHT models (Eng/Acvrl1 mutant mouse) |
| huntington_disease | UP / reduce (clinical) | SOD1-lowering antisense oligonucleotide ← sod1_amyotrophic_lateral_sclerosis; TTR-lowering siRNA / antisense ← transthyretin_amyloidosis | striatal neuron survival / motor-behaviour response to HTT-lowering in an HTT-expansion model |
| mecp2_duplication_syndrome | DOWN / restrain (investigational) | — (orphan: no same-axis approved donor) | duplication-phenotype rescue vs MeCP2-lowering dose (with a window -- under-correction returns toward Rett-like loss) |
| menkes_disease | UP / replace (clinical) | — (orphan: no same-axis approved donor) | serum copper / cuproenzyme response to parenteral copper-histidine |
| nephrogenic_diabetes_insipidus_x_linked | UP / correct (investigational) | — (orphan: no same-axis approved donor) | urine osmolality / AQP2 membrane insertion response to a V2R pharmacochaperone in a misfolding-AVPR2 model or patient |
| rho_autosomal_dominant_retinitis_pigmentosa | UP / reduce (clinical) | SOD1-lowering antisense oligonucleotide ← sod1_amyotrophic_lateral_sclerosis; TTR-lowering siRNA / antisense ← transthyretin_amyloidosis | photoreceptor survival / ERG response to allele-specific RHO knockdown in a P23H adRP retina |
| usher_syndrome_type_2a | UP / correct (clinical) | — (orphan: no same-axis approved donor) | ellipsoid-zone-width / visual-field / ERG trajectory under ultevursen vs sham in exon-13-mutant photoreceptors (e.g. patient iPSC-derived or animal model; the LUNA-style endpoint) |
| x_linked_retinitis_pigmentosa | UP / replace (clinical) | subretinal AAV gene replacement ← leber_congenital_amaurosis_2 | ERG, OCT outer-nuclear-layer thickness, microperimetry / static-perimetry sensitivity response to AAV-RPGR in RPGR-deficient retina (Rpgr-knockout mouse, RPGR-mutant dog, patient) |
What this is (and the firewall)
The kit is a method check, not a discovery engine. It re-derives the DIRECTION of already-known interventions from DNA-emergence structure under a strict firewall: promoter structure is read [V], the corrective axis direction is forced and cited [F], and all magnitude — efficacy, dose, safety — is ungraded [O]. The repurposing rows whose recipient already pursues the donor class are confirmatory sanity checks.
- [V] promoter / switch structure is computed from sequence.
- [F] the corrective-axis direction (UP/DOWN) is forced and cited.
- [O] no magnitude: no dose, potency, efficacy, response rate, or individual medical advice.