DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for fumaric aciduria — 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 moduleFumaric aciduria 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 fumaric aciduria 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
fumarate hydratase (FH) — FH 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 +drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 36AD · 2.11 Å · ligand L(+)-TARTARIC ACID (TLA). Experimental structure, not a prediction.
What the evidence adds up to
Fumaric aciduria is an autosomal recessive disorder caused by deficient activity of fumarate hydratase. In a 2006 case report, a girl with novel FH gene mutations had fibroblast FH activity of 1.9 nmol/min/mg protein, compared to controls of 40–80. She excreted fumaric acid at 217 and 445 mmol/mol creatinine at age 8. Her phenotype was described as relatively mild: she could sit at 1.5 years, walk with assistance at 4 years, and had speech limited to a few disyllables. She had hypotonia since birth, short apnoeic crises at 2 months, leg and arm spasms, grand mal seizures twice, ataxia with spastic paraparesis, and facial dysmorphism including depressed nasal bridge, anteverted ears, hypertelorism, and microcephaly. Brain MRI showed slight ventriculomegaly, white-matter atrophy, and hypoplasia of the corpus callosum. The family had a tumour predisposition: the mother and grandmother had uterine myomas, and the paternal grandfather and his two brothers died from lung and laryngeal cancers.
A 2021 case report described a Sri Lankan boy referred at 10 months with poor weight gain, hypotonia, global developmental delay, dysmorphic features (prominent forehead, low-set ears, micrognathia, hypertelorism), and persistent neutropenia. Urine organic acid assay showed massive elevation of fumaric acid on two occasions. Molecular analysis found a homozygous likely pathogenic missense variant, c.1048C>T p.(Arg350Trp), in the FH gene. He was the first molecularly diagnosed patient in Sri Lanka. A corrigendum corrected the title of that paper from “Urine Organic Analysis” to “Urine Organic Acid Analysis”.
No treatment or drug intervention is described in any of these abstracts. The 2006 report notes that some FH gene mutations have been associated with inherited cutaneous and uterine leiomyomas and papillary renal cell cancer, but no cancer surveillance or management data are given for the patients. What is missing is any clinical trial of a therapy, any systematic collection of long-term outcomes across a cohort, and any stratification by genotype or residual enzyme activity that might predict prognosis.
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 · 2006 · 23 citations · open access
Fumaric aciduria: Mild phenotype in a 8‐year‐old girl with novel mutations
AbstractFumaric aciduria is a rare, autosomal recessive disorder caused by deficient activity of fumarate hydratase (FH). Common clinical features are hypotonia, failure to thrive, severe psychomotor retardation and seizures. Facial dysmorphism and brain malformations are frequent. Recently, some FH gene mutations have been associated with inherited cutaneous and uterine leiomyomas and papillary renal cell cancer. Our patient had a relatively mild phenotype, a previously not reported genotype and familial tumour predisposition. The mother and grandmother had uterine myomas. The paternal grandfather and his two brothers died from lung and laryngeal cancers. The pregnancy was complicated by bleeding and intrauterine growth retardation. Delivery was after 35 weeks, with normal Apgar score. The girl was hypotonic since birth. At age 2 months the parents noticed short apnoeic crises. She could sit at age 1.5 years, and walk with assistance at 4 years. At age 8 years highly increased excretion of fumaric acid was found twice (217 and 445 mmol/mol creatinine). Shortly before that the girl started to have leg and arm spasms. Grand mal seizures occurred twice. Facial dysmorphism included depressed nasal bridge, anteverted ears, hypertelorism and microcephaly. Speech was limited to few disyllables. She was atactic with spastic paraparesis. Brain MRI showed slight ventriculomegaly, white-matter atrophy and hypoplasia of corpus callosum. Activity of FH in fibroblasts was 1.9 nmol/min/mg protein (controls 40-80). Analysis of the FH gene revealed the maternally derived c.1029_1031delAGT mutation, resulting in Val deletion and substitution of Gln by His, and paternally derived c.976C > T mutation, resulting in substitution of Pro by Ser.
Urine Organic Acid Analysis: Key Diagnostic Test for Fumaric Aciduria in a Sri Lankan Child
AbstractFumaric aciduria resulting from fumarate hydratase deficiency is a rare inherited disorder of the Krebs tricarboxylic acid cycle that is characterized by neurologic manifestations, a spectrum of brain abnormalities, and the excretion of fumaric acid in urine. We describe a 3 year old Sri Lankan boy who was referred at age 10 months with poor weight gain and hypotonia for further laboratory investigations. In addition to global developmental delay, there were noticeable dysmorphic features with a prominent forehead, low-set ears, micrognathia, and hypertelorism with persistent neutropenia. Urine organic acid assay revealed a massive elevation of fumaric acid on 2 occasions. Molecular analysis revealed a homozygous likely pathogenic missense variant, NM000143.3:c.1048C>T p. (Arg350Trp), in the FH gene, confirming the biochemical diagnosis. Our patient was the first patient in Sri Lanka molecularly diagnosed with fumaric aciduria. This case study highlights the importance of performing organic acid assays in children presenting with neurologic manifestations especially when these are suspected to have a metabolic basis.
Laboratory Medicine · 2021 · 0 citations · open access
Corrigendum to: Urine Organic Acid Analysis: Key Diagnostic Test for Fumaric Aciduria in a Sri Lankan Child
AbstractIn “Urine Organic Analysis: Key Diagnostic Test for Fumaric Aciduria in a Sri Lankan Child” (https://doi.org/10.1093/labmed/lmab083), there was an error in the title. This should read “Urine Organic Acid Analysis: Key Diagnostic Test for Fumaric Aciduria in a Sri Lankan Child” instead of “Urine Organic Analysis: Key Diagnostic Test for Fumaric Aciduria in a Sri Lankan Child”. This error has now been corrected online.
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.
