DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for tyrosinemia — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTyrosinemia maps to a 3-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
approvedNitisinoneApproved drug
Structures already discussed alongside tyrosinemia in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
tyrosine aminotransferase (TAT) — TAT is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has pyridoxal-5'-phosphate bound in it, shown as sticks.
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
In hereditary tyrosinemia, erythrocyte porphobilinogen synthase activity in patients was less than 5% of control values, and liver activity was less than 1% of reported normal activity. An inhibitor isolated from patient urine was identified as succinylacetone; fresh urine also contained succinylacetoacetate. The authors proposed that these metabolites originate from maleylacetoacetate or fumarylacetoacetate, that their accumulation indicates a block at the fumarylacetoacetase step, and that the primary enzyme defect may be decreased activity of fumarylacetoacetase. They suggested the severe liver and kidney damage might be due to accumulation of these tyrosine metabolites.
A cost–consequence analysis of nitisinone treatment for tyrosinemia type I in Quebec compared three historical groups: no nitisinone (1984–1994), late intervention (first dose 1994–1997), and early intervention (first dose 1997–2008). Nitisinone treatment was associated with reductions in number and duration of hospital admissions, paediatric intensive care admissions, and liver transplants. Hospitalisation cost per person-year was $12,980 in the no-nitisinone group, $5,590 in the late-intervention group, and $673 in the early-intervention group (p < 0.001). Hospital costs per person-year for liver transplant were $5,044 in the no-nitisinone group and $3,198 in the late-intervention group; there were no transplants in the early-intervention group. Nitisinone cost per person-year was $51,493 for early intervention and $64,895 for late intervention. The authors concluded that nitisinone improved outcomes while decreasing health care resource use and associated costs.
A 2024 Mexican consensus on tyrosinemia type 1, reached by experts including paediatric gastroenterologists, inborn error of metabolism specialists, geneticists, nutritionists, and a transplant surgeon, produced 32 statements voted on by Delphi method. The consensus covered epidemiology, clinical presentation, diagnosis, nutritional and medical treatment, and genetic counselling. It was intended as a tool for primary care physicians, paediatricians, and paediatric gastroenterologists to aid prompt diagnosis and treatment. A separate case report from Inner Mongolia noted that misdiagnosis of tyrosinemia is common due to low incidence and diagnostic difficulty, and aimed to raise clinical awareness.
What is still missing is prospective data on long-term outcomes beyond the historical Quebec cohort, which compared groups from different eras rather than randomising treatment. The cost of nitisinone itself remains high, and no controlled trial has tested whether early initiation prevents all liver complications, including hepatocellular carcinoma, in every patient. Patient stratification by genotype or age at diagnosis is not yet standardised in treatment protocols.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Proceedings of the National Academy of Sciences · 1977 · 456 citations · open access
On the enzymic defects in hereditary tyrosinemia.
AbstractThe activity of the enzyme porphobilinogen synthase (EC 4.2.1.24) in erythrocytes from patients with hereditary tyrosinemia was less than 5% of that in a control group and the activity in liver tissue was less than 1% of the reported normal activity. Urine from patients with hereditary tyrosinemia contained an inhibitor that was isolated and identified as succinylacetone (4,6-dioxoheptanoic acid) by gas/liquid chromatography-mass spectrometry. Fresh urine samples contained succinylacetoacetate (3,5-dioxooctanedioic acid) as well as succinylacetone. The inhibition of porphobilinogen synthase explains the high excretion of 5-aminolevulinate observed in hereditary tyrosinemia. Succinylacetone and succinylacetoacetate presumably originate from maleylacetoacetate or fumarylacetoacetate, or both, and their accumulation indicates a block at the fumarylacetoacetase (EC 3.7.1.2) step in the degradation of tyrosine. We suggest that the severe liver and kidney damage in hereditary tyrosinemia may be due to the accumulation of these tyrosine metabolites and that the primary enzyme defect in hereditary tyrosinemia may be decreased activity of fumarylacetoacetase.
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.
The Tohoku Journal of Experimental Medicine · 1968 · 7 citations · open access
Dietary Treatment of Infantile Tyrosinemia
AbstractAn infantile case of tyrosinemia was described. The treatment with a diet low in tyrosine and phenylalanine was started at the age of five months. During ten months of the treatment, almost complete disappearance of clinical symptoms and signs, such as failure to thrive and hepatic and renal damages, was attained. It was suggested that an appropriate intake of tyrosine and phenylalanine ranged from 30 to 40mg/kg/day for dietary control of tyrosinemia in infancy. It was also pointed out that over-restriction of tyrosine and phenylalanine might cause a failure to gain weight and an increased susceptibility to infections.
Boletín Médico del Hospital Infantil de México · 2024 · 0 citations · open access
Consenso mexicano de tirosinemia tipo 1
AbstractINTRODUCTION: Tyrosinemia type 1 is a rare disease with autosomal recessive inheritance, featuring various clinical manifestations. These may encompass acute neonatal liver failure, neonatal cholestatic syndrome, chronic hepatitis, cirrhosis, hepatocellular carcinoma, and, alternatively, kidney disorders like renal tubular acidosis, Fanconi syndrome, hypophosphatemic rickets, among other alterations. Diagnosis relies on detecting toxic metabolites in the blood and urine, ideally confirmed through molecular testing. METHOD: A consensus was reached with experts in the field of inborn errors of metabolism (EIM), including eight pediatric gastroenterologists, two EIM specialists, two geneticists, three pediatric nutritionists specialized in EIM, and a pediatric surgeon specializing in transplants. Six working groups were tasked with formulating statements and justifications, and 32 statements were anonymously voted on using the Likert scale and the Delphi method. The first virtual vote achieved an 80% consensus, with the remaining 20% determined in person. RESULTS: The statements were categorized into epidemiology, clinical presentation, diagnosis, nutritional and medical treatment, and genetic counseling. CONCLUSIONS: This consensus serves as a valuable tool for primary care physicians, pediatricians, and pediatric gastroenterologists, aiding in the prompt diagnosis and treatment of this disease. Its impact on the morbidity and mortality of patients with tyrosinemia type 1 is substantial.
Discussion of Clinical Cases · 2015 · 0 citations · open access
Tyrosinemia
AbstractA case of pediatric tyrosinemia in the Third Affiliated Hospital of Inner Mongolia Medical University was collected and analyzed on the basis of diagnosis, physical examination and treatment. Misdiagnosis of tyrosinemia is very common due to the low incidence, rare clinical cases and diagnosis difficulty. So this paper aims to arouse the doctors’ awareness of tyrosinemia during clinical practice.
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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