DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for triosephosphate isomerase 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 moduleTriosephosphate isomerase 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 triosephosphate isomerase 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
triosephosphate isomerase 1 (TPI1) — TPI1 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 g3pdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9FFC · 1.25 Å · ligand SN-GLYCEROL-3-PHOSPHATE (G3P). Experimental structure, not a prediction.
What the evidence adds up to
Triosephosphate isomerase deficiency is caused by a specific point mutation in the TPI gene. In three patients from three separate families, genomic DNA sequencing showed the mutation TPI315C, changing amino acid 104 from glutamate to aspartate. This same defect has now been found in nine apparently unrelated families worldwide, making it the most common form of the disorder. The reason for this repetitive occurrence remains unexplained; other mutations causing the deficiency have been restricted to single families.
A case report from Tunisia describes a two-year-old girl, the first child of nonconsanguineous parents. She presented with neonatal onset of chronic hemolytic anaemia and recurrent lower respiratory infections, followed by progressive neurological impairment. The diagnosis was made only after her death, by measuring TPI enzyme levels in her parents, who showed intermediate deficiency. Molecular testing revealed both parents were heterozygous for the Glu105Asp mutation (the same amino acid change, numbered differently). The authors note that paediatricians should consider TPI deficiency in patients with haemolytic anaemia and other concurrent symptoms.
A 2020 paper discusses the glycolytic enzyme triosephosphate isomerase as a potential therapeutic target for drug development against pathogenic organisms. It describes the concept of directing pharmacological compounds to a selective interaction site on the enzyme, with the aim of saving resources in drug development or drug repositioning. This paper does not report any experimental results, clinical data, or testing in patients with TPI deficiency.
What is still missing is any clinical trial of a drug for triosephosphate isomerase deficiency, any preclinical testing of a compound in patient-derived cells or animal models, and any systematic effort to stratify patients by mutation type or disease severity. The field lacks funding for basic research into the mechanism of neurological damage and for any drug screening programme.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Hematology · 1995 · 32 citations
Triosephosphate isomerase deficiency: Repetitive occurrence of point mutation in amino acid 104 in multiple apparently unrelated families
AbstractThe molecular basis of triosephosphate isomerase (TPI) deficiency was studied in 3 patients from three separate families. In all 3 patients, genomic DNA directly sequenced after amplification by the polymerase chain reaction exhibited the point mutation TPI315C amino acid 104 Glu-->Asp. Although other mutations known to cause TPI deficiency have been restricted to single families, the amino acid 104 defect has now been described in nine apparently unrelated families throughout the world and is clearly the most frequently occurring form of the disorder. The basis of the repetitive occurrence of this mutation remains unexplained.
Fetal and Pediatric Pathology · 2014 · 15 citations
Hemolytic Anemia and Progressive Neurologic Impairment: Think About Triosephosphate Isomerase Deficiency
AbstractWe have reported the first Tunisian case of triosephosphate isomerase (TPI) deficiency in a 2-year-old girl. She was the first child of a nonconsanguineous couple. The disease included a neonatal onset of chronic hemolytic anemia, recurrent low-respiratory infections then progressive neurological involvement. The diagnosis was made after her death from the TPI values of her parents who exhibited intermediate enzyme deficiency. Molecular study of TPI genes showed that the father and the mother are heterozygous for Glu105Asp mutation. Pediatricians must be alert to the differential diagnosis in patients having hemolytic anemia and other concomitant manifestations.
Potential Site to Direct Selective Compounds in the Triosephosphate Isomerase for the Development of New Drugs
AbstractAbstract In the pharmaceutical industry, the development of selective drugs to an enzyme or the repositioning of commercial drugs, today, is booming. The glycolytic enzyme triosephosphate isomerase (TIM) has been used as a therapeutic target for the development of new drugs against various pathogenic organisms. Therefore, saving resources in the development of new drugs, by directing the interaction of pharmacological compounds to an interaction site with a high probability to be selective, represents an opportunity for researchers.
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.
