DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for tyrosinemia type II — screening already-approved drugs against its 2-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 II maps to a 2-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 ii 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
tyrosine aminotransferase (TAT) — TAT 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 plpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3DYD · 2.3 Å · ligand PYRIDOXAL-5'-PHOSPHATE (PLP). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided concern tyrosinemia type I, not tyrosinemia type II. No abstract in the set mentions tyrosinemia type II. Nitisinone is discussed only for tyrosinemia type I. In a cost–consequence analysis of 148 children treated in Quebec between 1984 and 2009, nitisinone combined with a low-tyrosine and low-phenylalanine diet was associated with significant reductions in hospital admissions, paediatric intensive care admissions, and liver transplants. Hospitalisation costs per person-year were $673 for early-intervention (first dose 1997–2008), $5,590 for late-intervention (first dose 1994–1997), and $12,980 for no nitisinone (p < 0.001). No liver transplants occurred in the early-intervention group; hospital costs per person-year for transplant were $3,198 in the late-intervention group and $5,044 in the no-nitisinone group. Nitisinone cost per person-year was $51,493 for early intervention and $64,895 for late intervention.
A systematic review of four studies (sample sizes 17 to 148) found consistent evidence that nitisinone is effective for tyrosinemia type I, and some evidence that earlier treatment (within the first one or two months of life) is associated with reduced need for liver transplantation, lower rates of renal dysfunction, fewer neurological crises, and fewer, shorter hospital admissions compared to later treatment. Post hoc analyses suggested an association between earlier treatment and fewer liver transplants (0% of 10–24 patients versus 25–60% of 4–15 patients), but no impact on neurological crises. No effect of treatment timing on mortality was found. Study quality was moderate to weak, with high risk of confounding and limited applicability to screening contexts.
One abstract reports identification of two FAH gene mutations in a family carrier of tyrosinemia type I: c.648C>G (p.Ile216Met) predicted benign but creating a potential donor splice site, and c.1159G>A (p.Gly387Arg) predicted probably damaging. No abstract provides data on tyrosinemia type II. What is missing is any clinical or preclinical evidence for nitisinone in tyrosinemia type II, as well as any trial design, patient stratification, or funding directed at that specific indication.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Evaluation of pre-symptomatic nitisinone treatment on long-term outcomes in Tyrosinemia type 1 patients: a systematic review
AbstractAbstract Background Tyrosinemia type 1 (TYR1) is a rare autosomal recessive disorder of amino acid metabolism that is fatal without treatment. With medication (nitisinone) and dietary restrictions outcomes are improved. We conducted a systematic review to investigate if treatment with nitisinone following screening provides better long-term outcomes than treatment with nitisinone following symptomatic detection. Methods We searched Web of Science, Medline, Pre-Medline, and Embase up to 23rd September 2016 for journal articles comparing clinical outcomes of TYR1 patients receiving earlier versus later nitisinone treatment. Two reviewers independently screened titles and abstracts, assessed full texts, and appraised study quality. Data extraction was performed by a single reviewer and checked by a second. Results We included seven articles out of 470 unique records identified by our search. The seven articles included four studies (three cohort studies and one cross-sectional study). Study sample sizes ranged from 17 to 148. There is consistent evidence that nitisinone is an effective treatment for TYR1, and some evidence that earlier treatment with nitisinone and dietary restrictions within the first one or 2 months of life is associated with reduced need for liver transplantation, lower rates of renal dysfunction, fewer neurological crises, and fewer, shorter hospital admissions compared to later treatment. However, study quality was moderate to weak, with high risk of confounding and applicability concerns to the screening context. We conducted post hoc analyses to address these issues. Results suggested an association between earlier treatment and fewer liver transplants (earlier treatment: 0% of 10â 24 patients; later treatment: 25â 60% of 4â 15 patients), but no impact on neurological crises. We found no effect of treatment timing on mortality in either the primary or post hoc analyses. Post hoc analyses of other health-related outcomes were not possible because of sample size or reporting. Conclusions There is some evidence from observational studies that earlier treatment with nitisinone might be beneficial but this is subject to bias. The applicability of our findings to the screening context or clinical practice is limited as not all early-treated patients were identified by screening and late-treated groups included patients born prior to the availability of nitisinone.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
