Validation: recovering the standard of care
In hundreds of diseases the corrective direction derived from untuned geometry independently recovers a treatment already in clinical use. Since gamma is never fitted, the agreement was not engineered, so each recovery validates the logic. The kit reports these as agreement with established practice, adds no dose, and makes no treatment claim of its own.
In 322 of 839 diseases the direction derived from pure geometry independently recovers a treatment already in clinical use. Because the geometry was never tuned, each recovery is a genuine validation signal for the logic — not a treatment claim by this kit.
Why a recovery counts as validation
The switch is built from promoter sequence with γ never fitted (see Method). When that untuned geometry then points the same way as an approved, mechanistically-understood medicine for the same disease, the agreement was not engineered in. Replicated across hundreds of independent diseases, these agreements are the main evidence that the corrective-direction logic is tracking real biology.
Recovered standards — a representative sample
| disease | gene | recovered agent (direction-concordant) |
|---|---|---|
| Alkaptonuria | HGD | HPD / 4-HPPD inhibitor (nitisinone / NTBC) |
| Acute intermittent porphyria OMIM 176000 | HMBS | ALAS1-knockdown siRNA (givosiran) |
| Atypical haemolytic uraemic syndrome | CFH | terminal-complement (anti-C5) monoclonal antibody (eculizumab; long-acting ravulizumab) |
| Achondroplasia OMIM 100800 | FGFR3 | CNP analogue (vosoritide) |
| Bardet-Biedl syndrome | BBS1 | MC4R agonist (setmelanotide / Imcivree) |
| Beta-thalassaemia | HBB | erythroid-maturation agent / activin-receptor ligand trap (luspatercept) |
| Spinal muscular atrophy | SMN1 | SMN2 splicing modifier (nusinersen -- ASO; risdiplam -- small molecule) |
| Wilson disease OMIM 277900 | ATP7B | copper chelator (penicillamine / trientine) |
| Phenylketonuria | PAH | PEGylated phenylalanine ammonia-lyase (pegvaliase) |
| Cystic fibrosis OMIM 219700 | CFTR | CFTR potentiator (ivacaftor) |
| Gaucher disease OMIM 230800 | GBA1 | enzyme replacement (imiglucerase, velaglucerase alfa, taliglucerase alfa) |
| Fabry disease OMIM 301500 | GLA | enzyme replacement (agalsidase beta, agalsidase alfa, pegunigalsidase alfa) |
| Pompe disease OMIM 232300 | GAA | enzyme replacement (alglucosidase alfa, avalglucosidase alfa) |
| Hereditary angioedema | SERPING1 | plasma-kallikrein inhibitor (lanadelumab mAb / ecallantide / berotralstat) |
| Sickle cell disease OMIM 603903 | HBB | BCL11A erythroid-enhancer disruption (exagamglogene autotemcel / exa-cel) |
| HADH hyperinsulinism | HADH | K-ATP-channel opening (diazoxide) suppressing the unregulated insulin-secretory drive |
| 5-alpha reductase deficiency | SRD5A2 | dihydrotestosterone replacement (topical/systemic) supplying the deficient androgen |
| Aromatic L-amino acid decarboxylase | DDC | AAV2-hAADC putaminal gene therapy (eladocagene exuparvovec) |
| Abetalipoproteinemia | MTTP | high-dose fat-soluble-vitamin substitution (vitamin E with A and K) supplying the deficient vitamins downstream of the MTTP lipoprotein-assembly defect |
| Aceruloplasminemia | CP | iron-chelation therapy (deferiprone or deferasirox) reducing the tissue iron accumulation of the ceruloplasmin-ferroxidase loss |
| Triple A / Allgrove syndrome | AAAS | adrenal glucocorticoid replacement supplying the deficient cortisol output |
| Acrodermatitis enteropathica | SLC39A4 | oral zinc (zinc sulfate/gluconate replacement supplying the dietary zinc the SLC39A4 transporter can no longer absorb) |
| Adenine phosphoribosyltransferase deficiency | APRT | xanthine oxidase inhibitor (allopurinol; febuxostat) -- reduces 2,8-dihydroxyadenine production |
| Adenosine deaminase deficiency | ADA | ex-vivo autologous CD34+ haematopoietic stem-cell gene therapy (ADA-gene-corrected autologous HSC; Strimvelis, EMA-approved 2016) -- DIRECT, restores the causal gene itself |
| ADPKD | PKD2 | vasopressin-V2-receptor antagonism (tolvaptan) lowering the cAMP-driven cystogenic drive |
| Congenital afibrinogenemia | FGA | fibrinogen-concentrate replacement therapy supplying the deficient fibrinogen clotting substrate |
| Arginine:glycine amidinotransferase | GATM | creatine monohydrate |
| Aicardi-Goutieres syndrome 5 | SAMHD1 | janus-kinase (JAK) inhibition opposing the constitutive type-I-interferon drive |
| Aicardi-Goutieres syndrome 2 | RNASEH2B | JAK1/2 inhibition (baricitinib) reducing the type-I-interferon signalling over-activation (approved for other inflammatory indications; direction-only repurposing hypothesis) |
| Aicardi-Goutieres syndrome 1 | TREX1 | JAK inhibition (baricitinib) reducing the type-I-interferon signaling drive downstream of the TREX1 defect |
| Alagille syndrome | JAG1 | ileal bile-acid transporter (IBAT/ASBT) inhibition (maralixibat) lowering the recirculating bile-acid load |
| Alpha-1-antitrypsin deficiency OMIM 613490 | SERPINA1 | alpha-1-antitrypsin augmentation (pooled human plasma A1AT) |
| Alpha-mannosidosis | MAN2B1 | recombinant human alpha-mannosidase enzyme replacement (velmanase alfa / Lamzede, FDA 2023-02-16, the first approved therapy for alpha-mannosidosis) -- DIRECT on the MAN2B1 gene product |
| Alport autosomal | COL4A3 | renin-angiotensin-aldosterone-system antagonism (ACE inhibition) lowering intraglomerular pressure |
| Alport autosomal | COL4A4 | renin-angiotensin-aldosterone-system antagonism (ACE inhibition) lowering intraglomerular pressure |
| Alport syndrome X-linked | COL4A5 | renin-angiotensin system antagonism (ACE inhibition) reducing glomerular hyperfiltration downstream of the COL4A5 basement-membrane defect |
| Autoimmune lymphoproliferative syndrome | FAS | mTOR inhibition (sirolimus) reducing the lymphoproliferative effector drive of the FAS apoptosis defect |
| Alternating hemiplegia of childhood | ATP1A3 | calcium-channel modulation (flunarizine) reducing the paroxysmal episode burden in the ATP1A3 Na/K-ATPase channelopathy |
| Andersen-Tawil syndrome | KCNJ2 | class-IC antiarrhythmic (flecainide) |
| Androgen insensitivity | AR | sex-steroid hormone replacement (supportive, after gonadectomy where indicated) |
| Apparent mineralocorticoid excess | HSD11B2 | mineralocorticoid-receptor antagonism (spironolactone-class) opposing the unopposed cortisol mineralocorticoid drive |
| DOCK8 deficiency / autosomal recessive hyper-IgE syndrome… | DOCK8 | allogeneic haematopoietic-stem-cell transplantation supplying DOCK8-competent lymphoid lineages, restoring immune function |
| Argininemia / arginase-1 deficiency | ARG1 | dietary protein restriction with nitrogen-scavenging therapy (lowering the arginine and ammonia load the deficient ARG1 arginase can no longer clear; pegzilarginase enzyme substitution under study) |
| Argininosuccinic aciduria | ASL | nitrogen scavenger (sodium phenylbutyrate / glycerol phenylbutyrate); arginine supplementation |
| Aromatase deficiency | CYP19A1 | oestrogen replacement therapy supplying the oestrogen the deficient CYP19A1 aromatase can no longer synthesise |
| Artemis-deficient severe combined immunodeficiency | DCLRE1C | allogeneic or lentiviral-gene-modified haematopoietic-stem-cell transplantation supplying Artemis-competent lymphoid lineages, reconstituting immunity |
| ARVC | DSG2 | beta-adrenergic antagonism with exercise restriction reducing the arrhythmic adrenergic drive |
| ARVC | DSP | beta-adrenergic antagonism with exercise restriction reducing the arrhythmic adrenergic drive |
This is a sample; the complete agreement set spans all 322 matching diseases, each carrying the agreement callout on its own page. Candidate-level, 147 of 233 surfaced rows are explicit rediscoveries.
Still not a prescription. A recovered match means the direction agrees with medicine an expert may already use under proper care. It does not authorise anyone to self-administer, and it adds no dose.