HSP 4 (SPAST) OMIM 182601

In HSP 4 (SPAST, OMIM 182601), 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: — Honest hold (no matched agent). 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 0.5245, γ 1.4485, spinodal 0.6710). 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 HSP 4 is an R19 double-well emerged from the real proximal-promoter DNA of SPAST. 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)
1.4485
barrier
0.5245
spinodal
0.6710
s_on / s_off
1.2035 / -1.2035
fragility
0.34
corrective polarity
clear
forced direction
raise s toward ON branch

Chemistry feasibility (DIRECTION only [O]). small-molecule recrossing of the fold is geometrically harder (barrier 0.5245 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).

h-restore (drive modulator)sign: decreasegeometric rank 0.34
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 excess stable axonal microtubule load from the SPAST spastin microtubule-severing loss does NOT relieve the disease branch in a SPAST model, the h-restore(clear) lever is refuted for this axis.
gamma-restore (stabiliser / chaperone)sign: Nonegeometric rank 0.00
Mechanism. N/A
Applies to. none (honest exclusion)
EXCLUDED: null allele -- no product to stiffen
Falsifier. If a folding-stabiliser/chaperone does NOT re-deepen the healthy well for a residual SPAST 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

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.statusphasemap
microtubule-dynamics modulation reducing the excess stable axonal microtubule load of the SPAST severing loss
Errico 2002 Hum Mol Genet 11:153 (spastin, the protein mutated in autosomal dominant); Hazan 1999 Nat Genet 23:296 (spastin, a new aaa protein, is altered)
decreasepreclinical1◇ in trials
⚠ 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.
elementgradebasis
R19 switch & cusp geometry (this page)[V] verifiedemerged from measured promoter γ of SPAST; deterministic, 2×sha256 identical
corrective direction[F] forcedforced by the cusp sign; falsifiable (see lever falsifiers)
mapped agents / leads[O] opendirection-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).