DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for maple syrup urine disease — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMaple syrup urine disease maps to a 4-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 maple syrup urine disease 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
branched chain keto acid dehydrogenase E1 subunit alpha (BCKDHA) — BCKDHA 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 tppdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2BFD · 1.39 Å · ligand THIAMINE DIPHOSPHATE (TPP). Experimental structure, not a prediction.
What the evidence adds up to
Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder caused by mutations in the BCKDHA, BCKDHB, DBT, or DLD genes, which encode subunits of the branched-chain alpha-ketoacid dehydrogenase complex. A 2014 study identified a new missense mutation in exon 5 of the BCKDHB gene (c.508C>T) in an infant who died at six months of age. The parents were heterozygous for this change, and a different missense mutation at the same codon had previously been predicted by in silico analysis to be deleterious. The report states that this amino acid change can cause classic MSUD.
A 2023 review article describes MSUD as a rare inherited disorder characterised by impaired catabolism of branched-chain amino acids, leading to accumulation of toxic substances. The review categorises MSUD into different types depending on the specific enzyme deficiency and covers clinical features, genetic basis, diagnostic methods, and management strategies. A separate 2023 case report discusses metabolic crisis in MSUD as an unusual complication of the disease.
No clinical trial data, response rates, or survival statistics beyond the single infant death are provided in these abstracts. No drug treatment is tested or reported. The 2023 review does not present original patient data or quantitative outcomes. What remains missing are prospective clinical trials, standardised protocols for managing metabolic crises, and any evidence linking specific genotypes to treatment response or prognosis in a systematic cohort.
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 Pediatric Endocrinology and Metabolism · 2014 · 12 citations
A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)
AbstractMaple syrup urine disease (MSUD) is an autosomal recessive metabolic disease caused by mutations in the BCKDHA, BCKDHB, DBT and DLD genes, which encode the E1α, E1β, E2 and E3 subunits of the branched chain α ketoacid dehydrogenase (BCKD) complex, respectively. This complex is involved in the metabolism of branched-chain amino acids. In this study, we analyzed the DNA sequences of BCKDHA and BCKDHB genes in an infant who suffered from MSUD and died at the age of 6 months. We found a new missense mutation in exon 5 of BCKDHB gene (c.508C>T). The heterozygosity of the parents for the mentioned nucleotide change was confirmed by direct sequence analysis of the corresponding segment. Another missense mutation has been found in the same codon previously and shown by in silico analyses to be deleterious. This report provides further evidence that this amino acid change can cause classic MSUD.
Zenodo (CERN European Organization for Nuclear Research) · 2023 · 0 citations · open access
Symptoms, Treatment, Complications as well as Prognosis of Classic Maple Syrup Urine Disease (MSUD), Metabolic Instability, Neurological Complications and Treatment Of Intermediate MSUD, Case Studies as well as Success Stories of Thiamine Responsive MSUD
Abstract<em>Maple Syrup Urine Disease (MSUD) is a rare inherited metabolic disorder </em><em>manifested</em><em> by the impaired </em><em>catabolism</em><em> of certain amino acids. This disorder </em><em>results in the collection of </em><em>toxic substances in the body, leading to a range of symptoms and complications. MSUD is </em><em>categorized </em><em>into different types </em><em>dependent </em><em>on the specific enzyme deficiencies involved in the disease. This review article aims to provide a comprehensive overview of the types of MSUD, </em><em>along with</em><em> their clinical features, genetic basis, diagnostic methods, and management strategies.</em>
Zenodo (CERN European Organization for Nuclear Research) · 2023 · 0 citations · open access
Symptoms, Treatment, Complications as well as Prognosis of Classic Maple Syrup Urine Disease (MSUD), Metabolic Instability, Neurological Complications and Treatment Of Intermediate MSUD, Case Studies as well as Success Stories of Thiamine Responsive MSUD
Abstract<em>Maple Syrup Urine Disease (MSUD) is a rare inherited metabolic disorder </em><em>manifested</em><em> by the impaired </em><em>catabolism</em><em> of certain amino acids. This disorder </em><em>results in the collection of </em><em>toxic substances in the body, leading to a range of symptoms and complications. MSUD is </em><em>categorized </em><em>into different types </em><em>dependent </em><em>on the specific enzyme deficiencies involved in the disease. This review article aims to provide a comprehensive overview of the types of MSUD, </em><em>along with</em><em> their clinical features, genetic basis, diagnostic methods, and management strategies.</em>
INDIGO (University of Illinois at Chicago) · 2023 · 0 citations · open access
sj-pdf-1-aic-10.1177_0310057X231183981 - Supplemental material for Metabolic crisis in maple syrup urine disease: an unusual complication of a rare disease: a case report
AbstractSupplemental material, sj-pdf-1-aic-10.1177_0310057X231183981 for Metabolic crisis in maple syrup urine disease: an unusual complication of a rare disease: a case report by Hemang P Doshi, Hemal H Vachharajani, Michael C Tchan, Mohamed A Nasreddine and Kate E Billmore in Anaesthesia and Intensive Care
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.
