DeCure for Childhood onset GLUT1 deficiency syndrome 2
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for childhood onset GLUT1 deficiency syndrome 2 — 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 moduleChildhood onset GLUT1 deficiency syndrome 2 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 childhood onset glut1 deficiency syndrome 2 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
solute carrier family 2 member 1 (SLC2A1) — SLC2A1 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 bngdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6THA · 2.4 Å · ligand nonyl beta-D-glucopyranoside (BNG). Experimental structure, not a prediction.
What the evidence adds up to
In two families, GLUT1 deficiency syndrome followed an autosomal recessive pattern: a severely affected boy inherited one mutated allele from his asymptomatic mother and a de novo mutation on the paternal allele, while two mildly affected sisters inherited mutations from asymptomatic consanguineous parents. Red blood cell glucose uptake residual activity, a surrogate of haploinsufficiency, correlated with clinical severity. A 2015 case report described a child with intractable epilepsy and a spontaneous novel mutation not previously reported; treatment with the ketogenic diet produced significant improvement in quality of life. A 2018 case described a girl whose seizures responded to carbamazepine, contrary to the usual assumption that seizures in GLUT1-DS are resistant to conventional antiepileptic drugs.
A 2023 prospective multicentre validation study in France enrolled 428 patients with clinical suspicion of GLUT1DS and 67 retrospectively diagnosed patients. The blood test METAglut1™, which quantifies GLUT1 on erythrocyte surfaces, was 80% sensitive and greater than 99% specific for diagnosis. Concordance with glycorrhachia (CSF glucose) was substantial, and the positive predictive value of METAglut1™ was slightly higher than that of glycorrhachia in the prospective cohort. The test identified patients with SLC2A1 mosaicism and variants of unknown significance. The authors concluded that METAglut1™ is a non-invasive diagnostic test that allows wider screening of children and adults, including those with atypical forms.
The diagnosis of GLUT1DS still relies on lumbar puncture for glycorrhachia and SLC2A1 gene analysis, which limits the number of patients who receive standard care. The blood test METAglut1™, while robust and specific, missed 20% of confirmed cases in the validation cohort. What remains missing is independent replication of the blood test’s performance in larger, more diverse populations, prospective studies comparing it directly to long-term clinical outcomes, and evidence that earlier diagnosis via this test changes disease course or treatment response. No trial has yet tested whether screening with METAglut1™ improves patient stratification or reduces diagnostic delay in practice.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 2010 · 96 citations · open access
Glut1 deficiency: Inheritance pattern determined by haploinsufficiency
AbstractTwo families manifesting Glut1 deficiency syndrome (DS) as an autosomal recessive trait are described. In 1 family, a severely affected boy inherited a mutated allele from his asymptomatic heterozygous mother. A de novo mutation developed in the paternal allele, producing compound heterozygosity. In another family, 2 mildly affected sisters inherited mutations from their asymptomatic heterozygous consanguineous parents. Red blood cell glucose uptake residual activity, a surrogate of haploinsufficiency, correlated with the clinical severity. These cases demonstrate that Glut1 DS may present as an autosomal recessive trait. The clinical pattern of inheritance is determined by the relative pathogenicity of the mutation and the resulting degree of haploinsufficiency.
Refractory absence epilepsy associated with GLUT-1 deficiency syndrome
AbstractGLUT-1 deficiency syndrome (GLUT-1 DS) is a disorder of cerebral glucose transport associated with early infantile epilepsy and microcephaly. We report two boys who presented with refractory absence epilepsy associated with hypoglycorrhachia, both of whom have genetically confirmed GLUT-1 DS. We propose that these children serve to expand the phenotype of GLUT-1 DS and suggest that this condition should be considered as a cause of refractory absence seizures in childhood.
Prospective Multicenter Validation of a Simple Blood Test for the Diagnosis of Glut1 Deficiency Syndrome
AbstractObjective GLUT1 deficiency syndrome (Glut1DS) is a treatable neurometabolic disease that causes a wide range of neurological symptoms in children and adults. However, its diagnosis relies on an invasive test, i.e., a lumbar puncture (LP) to measure glycorrhachia, and, sometimes complex, molecular analyses of the <i>SLC2A1</i> gene. This procedure limits the number of patients able to receive the standard of care. We wished to validate the diagnostic performance of METAglut1™, a simple blood test that quantifies GLUT1 at the erythrocyte surface. Methods We performed a multicenter validation study in France, involving 33 centers. We studied two patient cohorts: a prospective cohort, consisting of patients with a clinical suspicion of Glut1DS explored through the reference strategy, i.e., LP and analyses of the <i>SLC2A1</i> gene; a retrospective cohort that included patients previously diagnosed with Glut1DS. All patients were blind-tested with METAglut1™. Results We analyzed 428 patients in the prospective cohort, including 15 patients newly diagnosed with Glut1DS, and 67 patients in the retrospective cohort. METAglut1™ was 80% sensitive and >99% specific for the diagnosis of Glut1DS. Concordance analyses showed a substantial agreement between METAglut1™ and glycorrhachia. In the prospective cohort, the positive predictive value of METAglut1™ was slightly higher than that of glycorrhachia. METAglut1™ succeeded to identify patients with Glut1DS with <i>SCL2A1</i> mosaicism and variants of unknown significance. Interpretation METAglut1™ is an easily performed, robust and non-invasive diagnostic test for the diagnosis of Glut1DS, which allows a wide screening of children and adults, including those with atypical forms of this treatable condition. Classification of Evidence This study provides class I evidence that a positive METAglut1™ test accurately distinguishes patients with suspected GLUT1 deficiency syndrome from other neurological syndromes as compared to invasive and genetic testing.
AbstractIntractable epilepsy is a common diagnosis among child neurology practitioners with medical management remaining unsatisfactory in many cases. GLUT1 deficiency syndrome (GLUT1-DS) is a disorder that should be considered in such situations. Evaluation by comparing serum to CSF glucose levels is a fast and relatively easy test, with hypoglycorrhachia being highly suggestive of GLUT1-DS. Furthermore, treatment with the ketogenic diet is well-established and can result in significant improvement in quality of life for these patients. The following case report outlines the presentation of one such patient and highlights common features that can be seen with GLUT1-DS. Of interest, she was found to have a spontaneous, novel mutation that has not been reported previously. Her case allows us to expand on the present literature and demonstrate the improvements that can be seen in a child with appropriate treatment.
GLUT1-DS in a Girl with Transitory Abnormal Eye Movements and Seizures Responding to Carbamazepine
AbstractIntroduction: Diagnosing GLUT1 deficiency syndrome (GLUT1-DS) is sometimes challenging because of its broad clinical spectrum. The diagnosis may be delayed when the first manifestations are considered as less typical for the disease. It is usually assumed, for instance, that seizures will be resistant to conventional antiepileptic drugs. Other clinical manifestations, such as early-onset abnormal eye movements, are probably under-recognized as a suggestive feature.
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.
