DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for encephalopathy due to GLUT1 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 moduleEncephalopathy due to GLUT1 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 encephalopathy due to glut1 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
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
GLUT1 deficiency syndrome is a brain energy failure syndrome caused by impaired glucose transport across brain tissue barriers, due to mutations in the SLC2A1 gene coding for the GLUT1 transporter. Over 200 cases of the classical form had been described by 2016, and by 2011 more than 100 patients were known worldwide. The biochemical hallmark is low cerebrospinal fluid glucose with normal blood glucose, giving a CSF-to-blood glucose ratio below 40–45%. Clinical features include eye-head movement abnormalities, seizures, neurodevelopmental impairment, deceleration of head growth, and movement disorders. The clinical spectrum has expanded to include paroxysmal exertional dyskinesia, early-onset absence epilepsy, and 1–2% of idiopathic generalised epilepsy.
Ketogenic diet therapies are the standard treatment and are described as effective, providing ketone bodies as an alternative fuel for brain energy metabolism. The 2020 international consensus statement from 23 experts gives Glut1DS-specific recommendations on diet duration, composition, and management. However, initial antiseizure drugs are often used before the diagnosis is made, and these drugs fail to treat the underlying metabolic disturbance during early brain development, contributing to long-term disease burden and impaired development of brain microvasculature. No alternative pharmacological treatments are mentioned in these abstracts as established therapy.
A 2025 study using astrocyte-specific and vascular endothelial cell-specific Glut1 haploinsufficient mice found that Glut1 is expressed throughout astrocytic branches, not only in endfeet. All Glut1-deficient mouse strains showed reduced glucose in both CSF and interstitial fluid, along with reduced cognitive and motor function compared to wild-type mice. The authors conclude that GLUT1 in astrocytes is implicated in the pathogenesis and that astrocytes may be a promising therapeutic target. Adeno-associated virus-based GLUT1 replacement therapy targeting vascular endothelial cells is noted as under development.
What remains missing are completed clinical trials of any drug or gene therapy for GLUT1 deficiency, patient registries with long-term natural history data, validated genotype-phenotype correlations, and any alternative treatment strategy that has been tested in humans beyond ketogenic diets. The 2020 consensus statement itself calls for better understanding of natural history throughout the life cycle and improved guidelines for early diagnosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
SANAMED · 2016 · 2 citations · open access
GLUT-1 deficiency: From pathophysilogy and genetics to abroad clinical spectrum
AbstractThe classical GLUT-1 deficiency syndrome (GLUT-1 DS, De Vivo disease) was described over 2 decades ago as a metabolic encephalopathy characterized by developmental delay, secondary microcephaly paroxysmal neurological symptoms (epilepsy) and movement disorders. The biochemical parameters of this disease, used in diagnosis, are low levels of glucose in the cerebrospinal fluid, normal level of glucose in the blood and consequent low ratio of cerebrospinal fluid vs. blood glucose levels (< 40-45%). So far, more than 200 cases of the classical GLUT-1 DS have been described in the literature. Genetic research demonstrated that this disease is caused by mutations in SLC2A1 gene coding for GLUT-1, a transporter of glucose across the blood brain barrier. Over the last few years the clinical spectrum of GLUT-1 deficiency was expanded to include other rare diseases such as paroxysmal exertional dyskinesia and early-onset absence epilepsy, but also some more common diseases such as idiopathic generalised epilepsy (1-2%). GLUT-1 deficiency is an important pathophysiological basis of the- se diseases as early diagnosis (aided by DNA mutation testing) and treatment (ketogenic diet) could lead to improved disease outcomes.
AbstractIn 1991 the first two patients with GLUT1 Deficiency were described. In 2011 over 100 patients are known worldwide. The disease has been recognized as an epileptic encephalopathy in children treatable with the ketogenic diet. Phenotype and genotype have become increasingly complex: mutations with sporadic, autosomal dominant, and autosomal recessive transmission as well as several hot spots in the SLC2A1 gene have been described. Recent years have seen the description of paroxysmal exertion-induced dystonia (PED), atypical absences, and non-epileptic paroxysmal events as a manifestation of GLUT1 Deficiency. Several animal models exist and the therapy knows several ketogenic diets. With the transmission of patients into adulthood long-term results are available. International parent support groups are active. Among future challenges will be patient registries, disease classifications, genotype-phenotype correlations and alternative treatment strategies.
Greater South Information System · 2020 · 0 citations · open access
Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group
AbstractGlut1 deficiency syndrome (Glut1DS) is a brain energy failure syndrome caused by impaired glucose transport across brain tissue barriers. Glucose diffusion across tissue barriers is facilitated by a family of proteins including glucose transporter type 1 (Glut1). Patients are treated effectively with ketogenic diet therapies (KDT) that provide a supplemental fuel, namely ketone bodies, for brain energy metabolism. The increasing complexity of Glut1DS, since its original description in 1991, now demands an international consensus statement regarding diagnosis and treatment. International experts (n = 23) developed a consensus statement utilizing their collective professional experience, responses to a standardized questionnaire, and serial discussions of wide-ranging issues related to Glut1DS. Key clinical features signaling the onset of Glut1DS are eye-head movement abnormalities, seizures, neurodevelopmental impairment, deceleration of head growth, and movement disorders. Diagnosis is confirmed by the presence of these clinical signs, hypoglycorrhachia documented by lumbar puncture, and genetic analysis showing pathogenic SLC2A1 variants. KDT represent standard choices with Glut1DS-specific recommendations regarding duration, composition, and management. Ongoing research has identified future interventions to restore Glut1 protein content and function. Clinical manifestations are influenced by patient age, genetic complexity, and novel therapeutic interventions. All clinical phenotypes will benefit from a better understanding of Glut1DS natural history throughout the life cycle and from improved guidelines facilitating early diagnosis and prompt treatment. Often, the presenting seizures are treated initially with antiseizure drugs before the cause of the epilepsy is ascertained and appropriate KDT are initiated. Initial drug treatment fails to treat the underlying metabolic disturbance during early brain development, contributing to the long-term disease burden. Impaired development of the brain microvasculature is one such complication of delayed Glut1DS treatment in the postnatal period. This international consensus statement should facilitate prompt diagnosis and guide best standard of care for Glut1DS throughout the life cycle.
Greater South Information System · 2020 · 0 citations · open access
Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group
AbstractGlut1 deficiency syndrome (Glut1DS) is a brain energy failure syndrome caused by impaired glucose transport across brain tissue barriers. Glucose diffusion across tissue barriers is facilitated by a family of proteins including glucose transporter type 1 (Glut1). Patients are treated effectively with ketogenic diet therapies (KDT) that provide a supplemental fuel, namely ketone bodies, for brain energy metabolism. The increasing complexity of Glut1DS, since its original description in 1991, now demands an international consensus statement regarding diagnosis and treatment. International experts (n = 23) developed a consensus statement utilizing their collective professional experience, responses to a standardized questionnaire, and serial discussions of wide-ranging issues related to Glut1DS. Key clinical features signaling the onset of Glut1DS are eye-head movement abnormalities, seizures, neurodevelopmental impairment, deceleration of head growth, and movement disorders. Diagnosis is confirmed by the presence of these clinical signs, hypoglycorrhachia documented by lumbar puncture, and genetic analysis showing pathogenic SLC2A1 variants. KDT represent standard choices with Glut1DS-specific recommendations regarding duration, composition, and management. Ongoing research has identified future interventions to restore Glut1 protein content and function. Clinical manifestations are influenced by patient age, genetic complexity, and novel therapeutic interventions. All clinical phenotypes will benefit from a better understanding of Glut1DS natural history throughout the life cycle and from improved guidelines facilitating early diagnosis and prompt treatment. Often, the presenting seizures are treated initially with antiseizure drugs before the cause of the epilepsy is ascertained and appropriate KDT are initiated. Initial drug treatment fails to treat the underlying metabolic disturbance during early brain development, contributing to the long-term disease burden. Impaired development of the brain microvasculature is one such complication of delayed Glut1DS treatment in the postnatal period. This international consensus statement should facilitate prompt diagnosis and guide best standard of care for Glut1DS throughout the life cycle.
The International Journal of Neuropsychopharmacology · 2025 · 0 citations · open access
ELUCIDATION OF THE INVOLVEMENT OF ASTROCYTE FUNCTION IN THE PATHOGENESIS OF GLUT1 DEFICIENCY SYNDROME
AbstractAbstract Background Glucose is a main energy source to support healthy brain function. Glucose transporter-1 (GLUT1) is the most important transport protein that transports glucose from the blood to the brain parenchyma and is reported to be expressed mainly in vascular endothelial cells and astrocyte endfeet. GLUT1 deficiency syndrome (GLUT1-DS) is a metabolic encephalopathy caused by impaired glucose transport into the brain. GLUT1-DS is a congenital disorder and heterozygous de novo mutations in the GLUT1 gene (SLC2A1) have been found in the majority of patients with GLUT1-DS, hypoglycaemia within the central nervous system, resulting in a range of CNS dysfunctions, including cognitive and motor dysfunction. Several papers have reported that Glut1 expressed in vascular endothelial cells (ECs) is important in neurological symptoms, and Adeno-associated virus (AAV)-based GLUT1 replacement therapy targeting vascular ECs is under development. Methods Astrocyte- and vascular EC-specific and systemic Glut1 haploinsufficient mice were used to attempt to identify the cells involved in the development of GLUT1-DS symptoms. Specifically, Aldh1l1-cre; Glut1 fl/+ mice were selected to analyze the contribution of astrocytes to GLUT1-DS symptoms and Tie2-cre; Glut1 fl/+ mice to analyze the contribution of ECs. Each mouse strain was used to measure glucose concentrations in cerebrospinal fluid (CSF) and interstitial fluid (ISF). These mice were also used in behavioral tests to assess cognitive and motor function, followed by evaluation of inflammation in the brain. Results First, Glut1 was found to be expressed throughout the astrocytic branches, not only in the endfeet. Next, compared to wild-type mice, all Glut1-deficient mouse strains showed reduced glucose levels in both CSF and ISF in addition to reduced cognitive and motor function. (All Glut1-deficient mouse strains: Aldh1l1-cre; Glut1 fl/+ mice, Tie2-cre; Glut1 fl/+ mice, Glut1 haploinsafficient mice). Conclusion These results suggest that Glut1 in astrocytes plays an important role in glucose uptake into CSF and ISF and in cognitive and motor functions. The two facts that Glut1 is expressed throughout astrocytes and the glucose concentration in ISF as well as CSF was reduced in Aldh1l1-cre; Glut1 fl/+ mice suggests that astrocytes may play a role in actively transporting glucose from blood to ISF. From this study, in addition to vascular ECs, GLUT1 in astrocytes is implicated in the pathogenesis of GLUT1-DS, suggesting that astrocytes may be a promising therapeutic target for GLUT1-DS.
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.
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