DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for tyrosinemia type III — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTyrosinemia type III maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for tyrosinemia type iii is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
4-hydroxyphenylpyruvate dioxygenase (HPD) — HPD is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet oxidanylidenedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8IM3 · 2.78 Å · ligand [1,3-diethyl-2,2-bis(oxidanylidene)-2$l^{6},1,3-benzothiadiazol-5-yl]-(1-methyl-5-oxidanyl-pyrazol-4-yl)methanone (92U). Experimental structure, not a prediction.
What the evidence adds up to
Tyrosinemia type III is an extremely rare disorder caused by a deficiency of 4-hydroxyphenylpyruvic dioxygenase. It has been associated with ataxia and mild mental retardation. The disorder is diagnosed by observing elevated tyrosine on plasma amino acid chromatography and elevated p-hydroxy-phenyl organic acids on urine organic acid analysis. Therapy consists of a diet low in phenylalanine and tyrosine. No drug treatment for tyrosinemia type III is described in these abstracts.
The drug nitisinone (also called NTBC, 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione) is discussed only for tyrosinemia type I, a different disorder caused by deficiency of fumarylacetoacetate hydrolase. In a cost-consequence analysis of all children with confirmed tyrosinemia type I treated in Quebec between 1984 and 2009, nitisinone combined with a low-tyrosine and low-phenylalanine diet was associated with significant reductions in the number and duration of hospital admissions, admissions to paediatric intensive care, and liver transplants. Hospitalisation costs per person-year were $673 for the early-intervention group (first dose between 1997 and 2008) and $5,590 for the late-intervention group (first dose between 1994 and 1997), compared to $12,980 for the no-nitisinone group (p < 0.001). No liver transplants occurred in the early-intervention group. The cost of nitisinone per person-year was $51,493 for early intervention and $64,895 for late intervention.
There is no evidence in these abstracts that nitisinone has been tested or used in tyrosinemia type III. The abstracts provide no data on any drug for this condition. What is missing is any clinical trial, any case series, or even a single patient report testing nitisinone or any other drug in tyrosinemia type III. The extreme rarity of the disorder makes trial design and patient stratification a fundamental obstacle, and no funding source for such work is mentioned.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part C Seminars in Medical Genetics · 2006 · 191 citations
The genetic tyrosinemias
AbstractThe genetic tyrosinemias are characterized by the accumulation of tyrosine in body fluids and tissues. The most severe form of tyrosinemia, Type I, is a devastating disorder of childhood that causes liver failure, painful neurologic crises, rickets, and hepatocarcinoma. This disorder is caused by a deficiency of fumarylacetoacetate hydrolase (FAH). If untreated, death typically occurs at less than 2 years of age, with some chronic forms allowing longer survival. It has a prevalence of about 1 in 100,000 newborns in the general population. Oculocutaneous tyrosinemia, Type II, is caused by a deficiency of tyrosine aminotransferase (TAT). It clinically presents with hyperkeratotic plaques on the hands and soles of the feet and photophobia due to deposition of tyrosine crystals within the cornea. Tyrosinemia Type III is an extremely rare disorder caused by a deficiency of 4-hydroxyphenylpyruvic dioxygenase. It has been associated with ataxia and mild mental retardation. These disorders are diagnosed by observing elevated tyrosine by plasma amino acid chromatography and characteristic tyrosine metabolites by urine organic acid analysis. In tyrosinemia Type I, methionine is also elevated, reflecting impaired hepatocellular function. Urine organic acids show elevated p-hydroxy-phenyl organic acids in each type of tyrosinemia, and the pathognomic succinylacetone in tyrosinemia Type I. Diagnosis can be confirmed by enzyme or molecular studies in tyrosinemia Type I. Therapy consists of a diet low in phenylalanine and tyrosine for each of the tyrosinemias and 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) for tyrosinemia Type I.
The Canadian Journal of Hospital Pharmacy · 2015 · 22 citations · open access
Cost–Consequence Analysis of Nitisinone for Treatment of Tyrosinemia Type I
AbstractBackground: Tyrosinemia type I is a rare but severe genetic metabolic disorder. Nitisinone combined with a diet low in tyrosine and phenylalanine became first-line therapy in 1994.Objectives: To estimate the direct medical costs of health care services related to the treatment of tyrosinemia type I, taking into consideration the real-life efficacy of nitisinone.Methods: A cost–consequence analysis was performed for all children with a confirmed diagnosis of tyrosinemia type I who were treated in Quebec between January 1, 1984, and January 1, 2009. The costs of care were compared for 3 consecutive historical groups: no nitisinone (1984 to 1994), late intervention with nitisinone (first dose received between 1994 and 1997), and early intervention with nitisinone (first dose received between 1997 and 2008). Data were derived from patient charts, hospital databases, and the Régie de l’assurance maladie du Québec and MED-ÉCHO administrative databases. Costs were reported in 2008 Canadian dollars.Results: Nitisinone treatment was associated with significant reductions in the number and duration of hospital admissions, the number of admissions to a pediatric intensive care unit, and the number of liver transplants. The cost of hospitalization per person-year was significantly lower in the 2 groups treated with nitisinone: $673 and $5 590 for the early-intervention and late-intervention groups, respectively, as compared to $12 980 for the no-nitisinone group (p < 0.001). Hospital costs per person-year for liver transplant were $3 198 for the late-intervention group and $5 044 for the no-nitisinone group: there were no transplants in the early-intervention group. The cost of nitisinone per person-year was $51 493 for the early-intervention group and $64 895 for the lateintervention group.Conclusions: Nitisinone treatment significantly improved the outcomes of patients with tyrosinemia type I, while decreasing utilization of health care resources, liver transplants, and associated costs.RÉSUMÉContexte : La tyrosinémie de type I est un trouble génétique du métabolisme rare, mais grave. La prise de nitisinone en association à un régime pauvre en tyrosine et en phénylalanine est devenue le traitement de première intention en 1994.Objectifs : Offrir une estimation des coûts médicaux directs des services de santé liés au traitement de la tyrosinémie de type I, tout en tenant compte de l’efficacité réelle de la nitisinone.Méthodes : Une analyse coûts-conséquences a été réalisée pour chaque enfant ayant reçu un diagnostic de tyrosinémie de type I et ayant été traité au Québec entre le 1er janvier 1984 et le 1er janvier 2009. Les coûts des soins ont été comparés entre trois groupes historiques se suivant dans le temps : sans nitisinone (de 1984 à 1994), traitement tardif à la nitisinone (première dose reçue entre 1994 et 1997) et traitement précoce à la nitisinone (première dose reçue entre 1997 et 2008). Les données ont été obtenues à partir de dossiers médicaux de patients, de bases de données d’hôpitaux, de la base de données administrative de la Régie de l’assurance maladie du Québec et de la banque de données ministérielles MED-ÉCHO. Les coûts sont indiqués en dollars canadiens de 2008.Résultats : L’on a associé le traitement par nitisinone à d’importantes réductions : du nombre d’hospitalisations et de la durée des séjours à l’hôpital, du nombre d’admissions à l’unité de soins intensifs pédiatrique et du nombre de greffes hépatiques. Les coûts d’hospitalisation (par personne-année) étaient beaucoup plus faibles dans les deux groupes traités par nitisinone : 673 $ et 5 590 $ respectivement pour le groupe de traitement précoce et le groupe de traitement tardif, contre 12 980 $ pour le groupe sans traitement par nitisinone (p < 0,001). Les coûts d’hospitalisation (par personne-année) pour les greffes hépatiques étaient de 3 198 $ pour le groupe de traitement tardif et de 5 044 $ pour le groupe sans traitement par nitisinone; le groupe de traitement précoce n’a fait l’objet d’aucune greffe hépatique. Les coûts du traitement par nitisinone (par personne-année) étaient de 51 493 $ pour le groupe de traitement précoce et de 64 895 $ pour le groupe de traitement tardif.Conclusions : Le traitement par nitisinone améliore grandement les résultats thérapeutiques des patients souffrant de tyrosinémie de type I et réduit également le recours aux ressources en santé et à la greffe hépatique, diminuant ainsi les coûts associés.
Case Reports in Genetics · 2012 · 6 citations · open access
Identification of Novel Mutations in FAH Gene and Prenatal Diagnosis of Tyrosinemia in Indian Family
AbstractCarrier of tyrosinemia type I was diagnosed by sequencing FAH (fumarylacetoacetate hydrolase) gene. It leads to the identification of heterozygous status for both c.648C>G (p.Ile216Met) and c.1159G>A (p.Gly387Arg) mutations in exons 8 and 13, respectively, in the parents. The experimental program PolyPhen, SIFT, and MT predicts former missense point mutation as "benign" that creates a potential donor splice site and later one as "probably damaging" which disrupts secondary structure of protein.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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