DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for citrullinemia type I — 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 moduleCitrullinemia type I 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 citrullinemia type i 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
argininosuccinate synthase 1 (ASS1) — ASS1 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 aspdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2NZ2 · 2.4 Å · ligand ASPARTIC ACID (ASP). Experimental structure, not a prediction.
What the evidence adds up to
Citrullinemia type I is a rare autosomal recessive disorder caused by mutations in the ASS1 gene, leading to elevated blood citrulline due to urea cycle malfunction. A 2022 study of nine Chinese infants with citrullinemia used next-generation sequencing to identify a novel ASS1 mutation (p.Leu313Met) and a rare ASS1 mutation (p.Thr323Ile, rs1250895424). Functional analysis showed both mutations significantly impaired ASS1 enzyme activity, with p.Thr323Ile clearly disrupting the interaction between ASS1 and protein arginine methyltransferase 7 (PRMT7). The same study also found a novel splicing mutation in SLC25A13 (c.1311 + 4_+7del), the gene responsible for citrin deficiency (citrullinemia type II), not type I. These findings expand the known mutational spectrum for ASS1 in the Chinese population but do not test any drug intervention.
A 2016 review on citrin deficiency (type II) notes that treatment differs from other urea cycle defects, requiring a high protein, low carbohydrate diet, with acute hyperammonemia responding to arginine therapy. Sodium pyruvate has been reported to provide benefit, and liver transplant fully corrects the type II phenotype. However, no abstract in this set describes a drug treatment specifically for citrullinemia type I. The 2022 genetic study does not address therapy, and the 2016 review concerns type II, not type I.
No drug is mentioned in these abstracts for citrullinemia type I. The available evidence is limited to genetic characterisation and general management principles for type II. What is missing is any clinical trial data for a repurposed drug in type I, adequate funding for such trials, and patient stratification based on the specific ASS1 mutations identified.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Genetics · 2022 · 5 citations · open access
Identification of Novel Mutations in Chinese Infants With Citrullinemia
AbstractCitrullinemia is a rare autosomal recessive disorder characterized by elevated concentrations of citrulline in the blood resulting from malfunction of the urea cycle. It is categorized into two types, types I and II, which are caused by argininosuccinate synthase 1 ( ASS1 ), and citrin ( SLC25A13 ) gene mutations, respectively. In this study, we performed genetic analysis on nine Chinese infants with citrullinemia using next-generation sequencing, which identified a novel mutation (p.Leu313Met) and a rare mutation (p.Thr323Ile, rs1250895424) of ASS1 . We also found a novel splicing mutation of SLC25A13 : c.1311 + 4_+7del. Functional analysis of the ASS1 missense mutations showed that both significantly impaired the enzyme activity of ASS1, with the p. Thr323Ile mutation clearly affecting the interaction between ASS1 and protein arginine methyltransferase 7 (PRMT7). These findings expand the mutational spectrum of ASS1 and SLC25A13 , and further our understanding of the molecular genetic mechanism of citrullinemia in the Chinese population.
Oxford University Press eBooks · 2016 · 0 citations
Citrin Deficiency
AbstractCitrin deficiency is an inborn error of metabolism that appears to affect both the urea cycle and energy generation. Worldwide, citrin deficiency is likely one of the commonest inborn errors of metabolism, 60,000–80,000 individuals are estimated to have citrin deficiency in China alone. Children typically present with an abnormal newborn screen or neonatal intrahepatic cholestasis with citrin deficiency (NICCD). Adults typically present clinically with neuropsychiatric symptoms, hepatic dysfunction and hyperammonemia. As plasma amino acids typically show an elevated citrulline at the time of crisis, this presentation is known as citrullinemia type II (CTLN2). Without therapy, cases may progress to liver failure. Individuals may also suffer recurrent pancreatitis. In contrast to other urea cycle defects, the treatment for citrin deficiency requires a high protein, low carbohydrate diet. Acute hyperammonemia responds to arginine therapy. Sodium pyruvate has been reported to provide benefit. In addition many cases will require restriction of galactose. Liver transplant fully corrects the CTLN2 phenotype.
DataSheet2_Identification of Novel Mutations in Chinese Infants With Citrullinemia.docx
Abstract<p>Citrullinemia is a rare autosomal recessive disorder characterized by elevated concentrations of citrulline in the blood resulting from malfunction of the urea cycle. It is categorized into two types, types I and II, which are caused by argininosuccinate synthase 1 (ASS1), and citrin (SLC25A13) gene mutations, respectively. In this study, we performed genetic analysis on nine Chinese infants with citrullinemia using next-generation sequencing, which identified a novel mutation (p.Leu313Met) and a rare mutation (p.Thr323Ile, rs1250895424) of ASS1. We also found a novel splicing mutation of SLC25A13: c.1311 + 4_+7del. Functional analysis of the ASS1 missense mutations showed that both significantly impaired the enzyme activity of ASS1, with the p. Thr323Ile mutation clearly affecting the interaction between ASS1 and protein arginine methyltransferase 7 (PRMT7). These findings expand the mutational spectrum of ASS1 and SLC25A13, and further our understanding of the molecular genetic mechanism of citrullinemia in the Chinese population.</p>
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.
