Mucopolysaccharidosis type VI (arylsulfatase B / N-acetylgalactosamine-4-sulfatase deficiency; Maroteaux-Lamy syndrome; MPS VI) OMIM 253200
In Mucopolysaccharidosis type VI (ARSB, OMIM 253200), the master switch sits on the ↓ DOWN branch (cited role × mechanism, below); the healthy state is the ON well. The forced corrective direction is to raise s toward ON branch (polarity: supply). 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 0.4084, γ 1.2782, spinodal 0.5562). The corrective direction is an interpretation of the model (a code output whose sign follows from the cited lesion role and mechanism); 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 Mucopolysaccharidosis type VI is an R19 double-well emerged from the real proximal-promoter DNA of ARSB. Its geometry is fixed by measured stiffness γ (never fitted); the numbers below are read directly off that cusp.
emergent axis
↓ DOWN (cited role × mechanism)
healthy branch
ON
lesion
LOF_null
γ (stiffness)
1.2782
barrier
0.4084
spinodal
0.5562
s_on / s_off
1.1306 / -1.1306
fragility
0.91
corrective polarity
supply
forced direction
raise s toward ON branch
Chemistry feasibility (DIRECTION only [O]). small-molecule recrossing of the fold is geometrically plausible (barrier 0.4084 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 — an interpretation of the model (code output, not a forced biological fact), and it is falsifiable. 2 lever families are derived; the lead is h-restore (drive modulator).
Mechanism. supply / restore the positive drive (replace-or-agonise the missing competence)
Applies to. allele-agnostic (downstream/environmental tilt)
favoured when the switch is fragile -- a small drive shift recrosses the fold
Falsifier. If supplying/agonising ARSB (raising the switch drive) does NOT move the DOWN switch toward the healthy branch in a ARSB-deficient model, the h-restore(supply) lever is refuted for this axis.
Falsifier. If a folding-stabiliser/chaperone does NOT re-deepen the healthy well for a residual ARSB 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: enzyme replacement therapy (galsulfase, recombinant human N-acetylgalactosamine-4-sulfatase / rhASB). The geometry recovered known medicine — this is a consistency check with established practice (partly by construction, since the corrective sign follows from the cited lesion class), 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).
agent (class)
dir.
status
phase
map
enzyme replacement therapy (galsulfase, recombinant human N-acetylgalactosamine-4-sulfatase / rhASB)
Turbeville 2011 (HSCT in MPS VI); AAV-ARSB preclinical
increase
clinical
3
◇ in trials
⚠ 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.
Class. enzyme replacement therapy (recombinant N-acetylgalactosamine-4-sulfatase / arylsulfatase B)
Mechanism. Infused to supply recombinant arylsulfatase B, replacing the lysosomal enzyme the ARSB gene can no longer make, so accumulated dermatan sulfate can be cleared. Direction: increase / restore the missing enzyme competence. Allele scope: agnostic -- replaces the downstream enzyme regardless of the ARSB variant. Pathway-specific to ARSB supply (mapped to MPS VI). An approved ERT; the geometry's supply direction recovers it.
✓ This is a rediscovery. Galsulfase is an approved ERT for MPS VI; the supply direction recovered the approved enzyme-replacement therapy.
Safety (qualitative; no magnitude). ERT class; infusion-reaction and anti-drug-antibody signals noted on label (qualitative; no magnitude)
Falsifier. If galsulfase (a pathway supply/increase agent) does NOT move the DOWN switch toward the healthy branch in a ARSB-deficient model, the h-restore(supply) direction is refuted for galsulfase 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)
code output
emerged from measured promoter γ of ARSB; deterministic, 2×sha256 identical
corrective direction
interpretation
code output of the model: the sign follows from the cited lesion role × mechanism (which well the disease occupies); falsifiable (see lever falsifiers); magnitude [O]
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 (read: consistency with established practice, partly by construction, since the corrective sign follows from the cited lesion class) -- the agent is already approved / established standard for this disease, so the direction logic agrees with 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).