In Isovaleric acidaemia (IVD, OMIM 243500), the master switch sits on the ↑ UP branch ([F] forced below); the healthy state is the ON well. The forced corrective direction is to raise s toward ON branch (polarity: clear). Classification: ✓ Recovers an existing standard. Direction only — no dose, no efficacy magnitude.
The disease maps to an R19 double-well whose corrective lever is read straight off the cusp (barrier 0.4821, γ 1.3886, spinodal 0.6298). The corrective direction is forced [F]; the agent names below are direction-concordant labels at grade [O] (no dose, no efficacy or safety magnitude). This is a research hypothesis offered to experts, not medical advice.
The emergence switch
The switch for Isovaleric acidaemia is an R19 double-well emerged from the real proximal-promoter DNA of IVD. Its geometry is fixed by measured stiffness γ (never fitted); the numbers below are read directly off that cusp.
emergent axis
↑ UP [F]
healthy branch
ON
lesion
LOF_null
γ (stiffness)
1.3886
barrier
0.4821
spinodal
0.6298
s_on / s_off
1.1784 / -1.1784
fragility
0.54
corrective polarity
clear
forced direction
raise s toward ON branch
Chemistry feasibility (DIRECTION only [O]). small-molecule recrossing of the fold is geometrically plausible (barrier 0.4821 at neutral drive; lower barrier = smaller drive to supply). [O] -- no affinity/potency/dose/efficacy asserted.
The derived corrective lever
The cusp forces a corrective direction: raise s toward ON branch. This is the load-bearing output of the framework — it is [F] forced, and it is falsifiable. 2 lever families are derived; the lead is h-restore (drive modulator).
Mechanism. remove / oppose the drive (clear the accumulating load that pins the disease branch)
Applies to. allele-agnostic (downstream/environmental tilt)
favoured when the switch is fragile -- a small drive shift recrosses the fold
Falsifier. If clearing/opposing the accumulating leucine does NOT relieve the disease branch in a IVD model, the h-restore(clear) lever is refuted for this axis.
Falsifier. If a folding-stabiliser/chaperone does NOT re-deepen the healthy well for a residual IVD allele (no rescue that a null allele lacks), the gamma-restore lever is refuted; null alleles are excluded by construction.
Agents mapped onto the lever
✓ Agreement with established practice. The corrective direction derived here (raise s toward ON branch) independently matches an agent already in clinical use for this disease: leucine-restricted diet (+ emergency catabolism protocol); glycine + L-carnitine conjugation therapy. The geometry recovered known medicine — this is a validation signal for the logic, not a new treatment claim by this kit.
Existing agents whose known action is direction-concordant with the derived lever (status as pinned in the corpus; no dose, no efficacy magnitude).
⚠ Mechanism-direction only — do not self-administer; no dose (unvalidated; set by a physician / national authority); not an approved use.
Direction-only candidate leads (corpus join)
Each lead is surfaced only because its known mechanism points the same way as the derived lever, and each comes with a source and a falsifier. None is a treatment.
Mechanism. An oral conjugating amino acid: glycine drives N-glycine conjugation of accumulated isovaleryl-CoA to isovalerylglycine, a non-toxic and readily renally-excreted adduct, lowering the free isovaleric acid that the IVD deficiency produces. Direction on the disease axis: decrease / clear the toxic organic-acid load. Engaged node: IVD. Allele scope: agnostic -- acts on the downstream metabolite irrespective of the IVD variant. Gene-specific to IVD (unique among the 113). An ACTIVE clearance lever, categorically distinct from the dietary-avoidance honest misses (which have no agent). Phenotype/metabolite-modifying, not a correction of the IVD lesion -- an established detoxification lever used with protein restriction and L-carnitine. The decrease direction recovers the established standard of metabolic management.
✓ This is a rediscovery. Glycine conjugation (forming excretable isovalerylglycine) is established standard metabolic management of isovaleric acidemia, alongside protein restriction and L-carnitine; lowering the toxic isovaleric-acid load is the disease-axis decrease direction, recovering the established standard. An active conjugation/clearance agent, distinct from the dietary-only honest misses. Phenotype/metabolite-modifying, not a correction of the IVD lesion.
Safety (qualitative; no magnitude). well tolerated as an oral conjugation agent within established organic-acidaemia management; used with protein restriction and L-carnitine (qualitative; no magnitude)
Falsifier. If glycine (a gene-specific decrease agent) clearing/opposing the accumulating load does NOT relieve the UP [F] disease branch in a IVD model, the h-restore(clear) direction is refuted for glycine here.
⚠ Mechanism-direction only — do not self-administer; no dose (unvalidated; set by a physician / national authority); not an approved use.
Evidence & provenance
What is reproduced vs. cited for this page.
element
grade
basis
R19 switch & cusp geometry (this page)
[V] verified
emerged from measured promoter γ of IVD; deterministic, 2×sha256 identical
corrective direction
[F] forced
forced by the cusp sign; falsifiable (see lever falsifiers)
mapped agents / leads
[O] open
direction-concordance only; corpus-pinned (2026-06-21); no dose, no efficacy/safety magnitude
Reading the agent column. VALIDATION SIGNAL -- the agent is already approved / established standard for this disease, so the direction logic recovered known clinical practice. Not a new claim by this kit. GENUINE HYPOTHESIS -- no approved indication for this disease; the direction match is a direction-only, untested [O] lead. Basis field grades the evidence (investigational here / in a related condition / off-label / speculative).