DeCure for COG7-congenital disorder of glycosylation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for COG7-congenital disorder of glycosylation — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCOG7-congenital disorder of glycosylation maps to a 2-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 cog7-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.
What the evidence adds up to
COG7-congenital disorder of glycosylation is one of several COG subunit deficiencies, but no abstract in this set specifically reports a COG7 patient. The 2009 study of a COG5 patient found that a homozygous splicing mutation (c.1669-15T>C) caused severely reduced COG5 protein expression, mild psychomotor retardation with delayed motor and language development, and a CDG phenotype with undersialylation of N- and O-glycans. Retrograde Golgi-to-endoplasmic reticulum trafficking was markedly delayed in the patient's fibroblasts after brefeldin-A treatment, and this delay was restored to normal by expressing wild-type COG5 cDNA. The authors note that COG deficiency should be considered even in children with mild neurological impairments.
A 2004 review states that by then 20 congenital disorders of glycosylation had been reported, with new ones appearing at nearly one per year since 1980. It recommends that CDG be considered in any child with an unexplained clinical syndrome. A 2021 review on treatment options across all CDG states that therapies remain limited and mostly symptomatic, though some novel approaches targeting the causative defect or secondary manifestations have moved from bench to bedside. A 2022 report describes a lethal COG6-CDG case in a neonate with skin scaling, erosions, joint contractures, and arachnodactyly, homozygous for a variant previously seen in Greek, Bulgarian, and Turkish individuals, suggesting a founder mutation in Southeastern Europe or West Asia.
No abstract in this set provides any treatment data, survival statistics, or response rates for COG7-CDG specifically. What is missing is any clinical trial or even a case series for COG7-CDG, any funding for natural history studies or drug screening in patient-derived cells, and any stratification of patients by residual COG complex function or specific mutation type.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Molecular Genetics · 2009 · 113 citations · open access
Deficiency in COG5 causes a moderate form of congenital disorders of glycosylation
AbstractThe conserved oligomeric Golgi (COG) complex is a tethering factor composed of eight subunits that is involved in the retrograde transport of intra-Golgi components. Deficient biosynthesis of COG subunits leads to alterations of protein trafficking along the secretory pathway and thereby to severe diseases in humans. Since the COG complex affects the localization of several Golgi glycosyltransferase enzymes, COG deficiency also leads to defective protein glycosylation, thereby explaining the classification of COG deficiencies as forms of congenital disorders of glycosylation (CDG). To date, mutations in COG1, COG4, COG7 and COG8 genes have been associated with diseases, which range from severe multi-organ disorders to moderate forms of neurological impairment. In the present study, we describe a new type of COG deficiency related to a splicing mutation in the COG5 gene. Sequence analysis in the patient identified a homozygous intronic substitution (c.1669-15T>C) leading to exon skipping and severely reduced expression of the COG5 protein. This defect was associated with a mild psychomotor retardation with delayed motor and language development. Analysis of different serum glycoproteins revealed a CDG phenotype with typical undersialylation of N- and O-glycans. Retrograde Golgi-to-endoplasmic reticulum trafficking was markedly delayed in the patient's fibroblast upon brefeldin-A treatment, which is a hallmark of COG deficiency. This trafficking delay could be restored to normal values by expressing a wild-type COG5 cDNA in the patient cells. This case demonstrates that COG deficiency and thereby CDG must be taken into consideration even in children presenting mild neurological impairments.
Current Opinion in Pediatrics · 2004 · 99 citations
Congenital disorders of glycosylation: a booming chapter of pediatrics
AbstractPURPOSE OF REVIEW: The detection and identification of new congenital disorders of glycosylation continues at a rapid pace. Sine June 2003, four new congenital disorders of glycosylation have been reported, making a total of 20 diseases (on average nearly 1 disease per year since the first report in 1980; 12 of these congenital disorders of glycosylation were identified in the past 6 years). RECENT FINDINGS: Three of these newly discovered CDG are caused by defects in early steps of dolichol-linked oligosaccharide biosynthesis. Affected patients have a neurologic or a multisystem disease. The fourth new CDG is a completely new CDG type caused by a defect in an endoplasmic reticulum-Golgi shuttle protein carrying multiple glycosyltransferases and nucleotide-sugar transporters. SUMMARY: Disorders of nearly all organs and systems have been reported and continue to be reported in congenital disorders of glycosylation. Therefore, it is strongly recommended that congenital disorders of glycosylation be considered in any child with an unexplained clinical syndrome.
Frontiers in Genetics · 2021 · 41 citations · open access
Treatment Options in Congenital Disorders of Glycosylation
AbstractDespite advances in the identification and diagnosis of congenital disorders of glycosylation (CDG), treatment options remain limited and are often constrained to symptomatic management of disease manifestations. However, recent years have seen significant advances in treatment and novel therapies aimed both at the causative defect and secondary disease manifestations have been transferred from bench to bedside. In this review, we aim to give a detailed overview of the available therapies and rising concepts to treat these ultra-rare diseases.
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.
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.
