DeCure for COG5-congenital disorder of glycosylation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for COG5-congenital disorder of glycosylation — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCOG5-congenital disorder of glycosylation maps to a 3-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 cog5-congenital disorder of glycosylation 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
HMG-box transcription factor 1 (HBP1) — HBP1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3QVE · 2.04 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In five patients with COG5-CDG, mass spectrometry profiling of serum glycans showed a significant increase in the aglycosylated O-glycoform apoC-III 0a and a significant decrease in the mono-sialylated O-glycoform apoC-III 1 compared with age-matched controls. The serum N-glycome in these patients was characterised by a relative abundance of undersialylated and undergalactosylated biantennary and triantennary glycans, along with a slight increase in high-mannose structures and hybrid glycans. These findings were reported in 2017 as a means to support clinical diagnosis by revealing novel aspects of O-glycan and N-glycan profiling in COG5-CDG.
A 2023 case report described the first COG5-CDG patient identified at the fetal stage, carrying a homozygous COG5 c.95T>G variant. Prenatal testing at 24 weeks of pregnancy revealed polyhydramnios, hydrocephaly, abnormal facial features, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, and short fetal femur and humerus lengths. The authors noted that homozygous patients had never been seen before in the literature for COG5-CDG.
The Frontiers in CDG Consortium, established in 2019, has enrolled over 300 CDG patients in a Natural History Study, discovered novel biomarkers, and launched clinical trials aiming to restore appropriate glycosylation and target newly identified disease mechanisms. However, the consortium’s own 2024 summary states that the underlying glycosylation disruptions and pathophysiologic mechanisms responsible for specific CDG clinical manifestations have been determined for only a few hypoglycosylated proteins, and that ongoing bottlenecks and knowledge gaps at the intersections of glycobiology and clinical care require further investigation.
What is still missing for COG5-CDG specifically is any published therapeutic trial, any drug tested in these patients, and any validated biomarker that tracks with clinical severity or response. The natural history data and glycoproteomic tools exist, but patient numbers remain extremely small, no stratified cohorts have been assembled for a trial, and no funding source has been committed to a repurposing screen or a targeted therapy for this single COG subunit defect.
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 Medical Genetics Part A · 2017 · 41 citations
Congenital disorders of glycosylation: The Saudi experience
AbstractWe retrospectively reviewed Saudi patients who had a congenital disorder of glycosylation (CDG). Twenty-seven Saudi patients (14 males, 13 females) from 13 unrelated families were identified. Based on molecular studies, the 27 CDG patients were classified into different subtypes: ALG9-CDG (8 patients, 29.5%), ALG3-CDG (7 patients, 26%), COG6-CDG (7 patients, 26%), MGAT2-CDG (3 patients, 11%), SLC35A2-CDG (1 patient), and PMM2-CDG (1 patient). All the patients had homozygous gene mutations. The combined carrier frequency of CDG for the encountered founder mutations in the Saudi population is 11.5 per 10,000, which translates to a minimum disease burden of 14 patients per 1,000,000. Our study provides comprehensive epidemiologic information and prevalence figures for each of these CDG in a large cohort of congenital disorder of glycosylation patients.
Lethal COG6‐CDG in neonatal patient with arachnodactyly, joint contractures, and skin manifestations: Founder mutation in the Southeastern European population?
AbstractHerein, we report a lethal case of the ultra-rare COG6-congenital disorder of glycosylation (CDG) presenting with skin manifestations (scaling and erosions) and joint contractures in a neonate of Albanian origin. The patient was homozygous for a COG6 pathogenic variant, previously reported in another three individuals of Greek, Bulgarian and Turkish descent. The presence of a founder mutation in the geographical area is possible. The index case emphasizes the need to consider CDGs in neonatal patients with skin manifestations and joint contractures, particularly patients of Southeastern European or West Asian origin.
Molecular Syndromology · 2023 · 4 citations · open access
The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant
AbstractIntroduction: Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. Case Presentation: In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column abnormality, macrocephaly, scoliosis, micrognathia, abnormal kidney morphology, short fetal femur length, and short fetal humerus length in the fetus. Whole-exome sequencing was performed; the COG5 gene has shown a pathogenic variant. Discussion: Homozygous patients have never been seen before in the literature for COG5-CDG. We demonstrate the first CDG patient at fetus stage with homozygous COG5 c.95T>G variant.
AbstractCongenital disorders of glycosylation (CDG) are a group of rare monogenic human disorders caused by defects in the genes encoding the proteins that generate, attach, and modify glycans, thus disrupting cellular glycosylation machinery. Over 200 CDG caused by disruptions of 189 different genes are currently known. The multi-system disease manifestations of the CDG disorders highlight the importance of glycosylation across the organ systems. Clinical manifestations of CDG tend to group among genes contributing to the same glycosylation pathways, suggesting shared pathophysiology related to the glycosylation disruptions. However, the underlying glycosylation disruptions and pathophysiologic mechanisms responsible for specific CDG clinical manifestations have been determined for only a few hypoglycosylated proteins. The Frontiers in CDG Consortium (FCDGC) is an international network of clinical sites, laboratories, and patient advocacy groups established in 2019 to improve clinical symptoms, quality of life, and life expectancy for individuals with CDG. FCDGC seeks to answer decades of unresolved questions, address knowledge gaps, develop and validate new biochemical diagnostic techniques and therapeutic biomarkers, and explore novel therapeutic options for CDG. Over the past 5 years, FCDGC has launched a Natural History Study with over 300 CDG patients, discovered novel biomarkers suggesting new mechanisms of disease, and launched clinical trials aiming to restore appropriate glycosylation and targeting newly identified potential mechanisms of disease. Technical advances in glycobiology are making it increasingly possible to comprehensively catalog glycoproteomic data and to probe functional impact of altered glycosylation. My laboratory applies glycoproteomic technologies to samples from human subjects and genetic model systems to identify glycosylation abnormalities and unlock new insights from translational glycobiology. Current findings and accomplishments highlight the ongoing bottlenecks and knowledge gaps at intersections of glycobiology and clinical care requiring further investigation.
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.
