DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for ornithine translocase deficiency — 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 moduleOrnithine translocase deficiency 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 ornithine translocase deficiency 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.
What the evidence adds up to
Ornithine transcarbamylase deficiency is an X-linked urea cycle disorder. Most cases are caused by novel, private mutations in the OTC gene, which makes standardised genetic screening impractical. Identifying the specific mutation is relevant for prenatal diagnosis, predicting clinical course, and future gene therapy. A 2010 case report describes a 13-year-old girl heterozygous for the hypomorphic R40H mutation who presented with hyperammonemic coma (ammonia 477 μmol/L) and elevated urinary orotate. She recovered after intravenous sodium benzoate and arginine and was discharged on a protein-restricted diet. At one year of follow-up she had one further hyperammonemic episode during an infection. A literature review found one other symptomatic female with the R40H mutation who died of hyperammonemic coma in her late teens. The authors conclude that even a mutation usually considered mild can cause fatal decompensation in female heterozygotes.
A 2024 review covers the full spectrum of the disorder, from neonatal onset in hemizygous males to later presentations in females and males with hypomorphic mutations. It states that untreated hyperammonemia leads to neurotoxicity, coma, and death. The review focuses on prenatal, natal, and postpartum care for carrier females and affected male newborns, and mentions lifelong and anticipated future treatments, but does not report any new clinical trial data or survival statistics. No drug other than sodium benzoate and arginine is discussed in the abstracts.
What is missing: no controlled trials of any therapy for ornithine transcarbamylase deficiency are reported. The 2010 case is a single patient with short follow-up. The 2024 review does not provide new efficacy data. There is no evidence on long-term outcomes, optimal dosing, or patient stratification beyond mutation type. Funding for prospective registries or randomised treatment comparisons is not described.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Inherited Metabolic Disease · 1997 · 49 citations
Identification of ‘private’ mutations in patients with ornithine transcarbamylase deficiency
AbstractThe majority of cases of ornithine transcarbamylase deficiency are due to novel mutations making it impossible to develop common methods for genetic analysis. However, identification of causative mutations has important implications for diagnosis (particularly prenatal diagnosis), prediction of likely course and outcome and the eventual possibility of gene therapy. As part of a continuing study of ornithine transcarbamylase deficiency, we now report an additional thirty novel mutations in the ornithine transcarbamylase gene, together with a brief summary of their clinical presentations.
Journal of Medical Case Reports · 2010 · 13 citations · open access
Female heterozygotes for the hypomorphic R40H mutation can have ornithine transcarbamylase deficiency and present in early adolescence: a case report and review of the literature
AbstractINTRODUCTION: Ornithine transcarbamylase deficiency is the most common hereditary urea cycle defect. It is inherited in an X-linked manner and classically presents in neonates with encephalopathy and hyperammonemia in males. Females and males with hypomorphic mutations present later, sometimes in adulthood, with episodes that are frequently fatal. CASE PRESENTATION: A 13-year-old Caucasian girl presented with progressive encephalopathy, hyperammonemic coma and lactic acidosis. She had a history of intermittent regular episodes of nausea and vomiting from seven years of age, previously diagnosed as abdominal migraines. At presentation she was hyperammonemic (ammonia 477 μmol/L) with no other biochemical indicators of hepatic dysfunction or damage and had grossly elevated urinary orotate (orotate/creatinine ratio 1.866 μmol/mmol creatinine, reference range <500 μmol/mmol creatinine) highly suggestive of ornithine transcarbamylase deficiency. She was treated with intravenous sodium benzoate and arginine and made a rapid full recovery. She was discharged on a protein-restricted diet. She has not required ongoing treatment with arginine, and baseline ammonia and serum amino acid concentrations are within normal ranges. She has had one further episode of hyperammonemia associated with intercurrent infection after one year of follow up. An R40H (c.119G>A) mutation was identified in the ornithine transcarbamylase gene (OTC) in our patient confirming the first symptomatic female shown heterozygous for the R40H mutation. A review of the literature and correspondence with authors of patients with the R40H mutation identified one other symptomatic female patient who died of hyperammonemic coma in her late teens. CONCLUSIONS: This report expands the clinical spectrum of presentation of ornithine transcarbamylase deficiency to female heterozygotes for the hypomorphic R40H OTC mutation. Although this mutation is usually associated with a mild phenotype, females with this mutation can present with acute decompensation, which can be fatal. Ornithine transcarbamylase deficiency should be considered in the differential diagnosis of unexplained acute confusion, even without a suggestive family history.
Ornithine Transcarbamylase Deficiency Presenting as Hepatitis
AbstractOrnithine transcarbamylase deficiency is an inborn error of metabolism that commonly presents as hyperammonemia in neonates. We present a case of a 2-year-old girl who was referred to a pediatric emergency department for evaluation of hepatitis, an uncommon presentation of ornithine transcarbamylase deficiency. Recognition of late presentations of this disease is important for survival and neurological outcome.
MCN The American Journal of Maternal/Child Nursing · 2024 · 0 citations
Maternal and Newborn Care for Ornithine Transcarbamylase Deficiency
AbstractABSTRACT: Ornithine transcarbamylase deficiency is the most common urea cycle disorder. If left untreated, pathogenic variants in the OTC gene can cause hyperammonemia leading to neurotoxicity, coma, and death. A comprehensive overview of ornithine transcarbamylase deficiency is presented including the genetic cause; varied age of onset, clinical presentation, and severity; diagnostic testing; and lifelong and anticipated future treatments. More specifically, there is a focus on the prenatal, natal, and postpartum course and treatment recommendations for genetic heterozygous (carrier) females and hemizygous male newborns with ornithine transcarbamylase deficiency.
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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