DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for beta-ketothiolase 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 moduleBeta-ketothiolase 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 beta-ketothiolase 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.
Molecular view
acetyl-CoA acetyltransferase 1 (ACAT1) — ACAT1 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 coadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2IBY · 1.85 Å · ligand COENZYME A (COA). Experimental structure, not a prediction.
What the evidence adds up to
Beta-ketothiolase deficiency is an inherited disorder of ketone body metabolism and isoleucine catabolism that typically manifests as recurrent ketoacidotic episodes. A 2016 review notes that diagnosis is complicated by atypical presentations and by other disorders, such as succinyl-CoA:3-oxoacid CoA transferase and 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiencies, which can mimic its clinical or biochemical signs. Final diagnosis requires enzymatic assay or molecular analysis, and screening programmes have identified an increasing number of patients, including some previously missed.
A 2017 case report describes identical male twins, aged 1 year 8 months, who presented with severe metabolic acidosis, hypoglycaemia, and altered sensorium following common viral illnesses. Both were diagnosed by urine gas chromatography-mass spectrometry. They responded to symptomatic treatment and were growing well on a protein-restricted diet. The report states that beta-ketothiolase deficiency has a favourable outcome if preventive measures are taken early.
A 2015 study of 35 patients in Vietnam, the largest single-centre cohort reported, found that 33 of 35 presented with a crisis of ketone acidosis. One case was diagnosed without symptoms at 3 days of age but developed a crisis at 6 months; one case remained asymptomatic at 5 years old. Mean age at first crisis was 13.1 months. During crises, 100% had severe ketone metabolic acidosis (pH 6.5–7.05) and leukocytosis. 94% recovered from the first crisis, and 79% had normal development. 20 of 35 patients had recurrent crises. Genetic analysis of 21 patients found homozygous or compound heterozygous mutations in the T2 gene; the R208X mutation accounted for 70% of mutant alleles in Vietnam.
What remains missing is a clear picture of long-term outcomes beyond early childhood, particularly for patients with recurrent crises or those identified only after neurological damage. No controlled trial of any specific treatment exists; management is limited to protein restriction and acute symptomatic care. The rarity of the disorder makes prospective trials difficult, and no data on adult outcomes or cognitive function in treated versus untreated patients are available.
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 Inborn Errors of Metabolism and Screening · 2016 · 24 citations · open access
Beta-Ketothiolase Deficiency
AbstractAbstract Beta-ketothiolase deficiency is an inherited disorder of ketone body metabolism and isoleucine catabolism. It typically manifests as recurrent ketoacidotic episodes with characteristic abnormalities in the urinary organic acid profile. However, several challenges in the diagnosis of beta-ketothiolase deficiency have been encountered: atypical presentations have been reported and some other disorders, such as succinyl-CoA:3-oxoacid CoA transferase and 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiencies, can mimic the clinical and/or biochemical signs of beta-ketothiolase deficiency. A final diagnosis of beta-ketothiolase deficiency requires an enzymatic assay and/or a molecular analysis, but some caveats must be considered. Despite the reported missed cases, screening programs have successfully identified an increasing number of patients with beta-ketothiolase deficiency. Early diagnosis and management of beta-ketothiolase deficiency will enable prevention of its serious acute and chronic complications and ultimately improve the prognosis.
Indian Journal of Child Health · 2017 · 0 citations · open access
A rare case of beta-ketothiolase deficiency in identical twins
AbstractBetaketothiolase deficiency is a rare defect of isoleucine and ketone body metabolism which manifests as severe metabolic acidosis following common viral illnesses. A set of 1 year, 8 month-old identical male twins presented with similar symptoms in different time frames. Both of them had severe metabolic acidosis, hypoglycemia, and altered sensorium. Both twins tested positive for beta-ketothiolase deficiency by urine gas chromatography-mass spectrometry. The children responded to symptomatic treatment and are now growing well on a protein-restricted diet. Beta-ketothiolase deficiency is a rare disorder of amino acid metabolism with a favorable outcome if preventive measures are taken early.
AB099. Beta ketothiolase deficiency: phenotype and genotype in Vietnam population
AbstractBACKGROUND AND OBJECTIVE: Beta ketothiolase (T2) deficiency is rare inherited metabolic disease worldwide. But it is the most common organic aciduria in Vietnam with 35 cases. To describe phenotypes, genotypes of T2 deficiency. METHODS: Descriptive study of 35 patients with T2 deficiency at National Hospital of Pediatrics-Hanoi-Vietnam from 2005 to 2012. A total of 21 cases from 19 families were analyzed of T2 gene. RESULTS: A total of 35 patients were born to 30 unrelated families and unconsanguinity parents. And 33/35 patients presented crisis of ketone acidosis. One case was diagnosed without symptom at 3 days of age but developed the crisis at 6 months of age. One case was asymptomatic until now (5 years old). Mean onset of the first crisis was 13.1 months. Clinical features of the crises were dehydration, tarchypnea, lethargy/coma and triggered by infections. Laboratory of the crises showed 100% severe ketone metabolic acidosis (pH: 6.5-7.05), leukocytosis. 94% cases recovered from the 1st crisis and 79% cases had normal development. A total of 20/35 patients had recurrent crisis. And 21/21 patients were found homozygous/compound heterozygous mutations of T2 gene. Five different mutations have been identified: R208X; IVS10-1g>c; A410V; 163_167del5ins2; c.1032-103 INS A. And R208X is the most common mutation in Vietnam (70% of mutant allele) as well as in the world. CONCLUSIONS: The biggest T2 deficiency patients were identified in a Vietnam center (account 1/3 total cases in the world). Worldwide, there are no common mutations of T2 gene found except common R208X mutation in Vietnam.
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.
