DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital disorder of glycosylation — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongenital disorder of glycosylation maps to a 37-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 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
alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT2) — MGAT2 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 udpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5VCM · 1.599 Å · ligand URIDINE-5'-DIPHOSPHATE (UDP). Experimental structure, not a prediction.
What the evidence adds up to
Despite advances in identifying congenital disorders of glycosylation, treatment options remain limited and are often constrained to symptomatic management of disease manifestations. A 2021 review states that recent years have seen significant advances in treatment and novel therapies aimed both at the causative defect and secondary disease manifestations transferred from bench to bedside, but it gives no concrete numbers for survival or response rates. A 2022 review similarly reports that treatment is usually symptomatic, with specific treatment only available for some of these disorders, and notes that there is no universal or pathognomonic sign or symptom and no sensitive diagnostic test.
A 2019 clinical observation describes a child with PMM2-CDG, the most commonly diagnosed type with about 800 cases worldwide. The diagnosis was based on a combination of clinical, laboratory, and instrumental data including characteristic phenotype, hyperinsulinism, delayed development, neurological manifestations, coagulopathy, liver damage, exudative enteropathy, and abnormal forms of transferrin. The authors report that for the first time they observed positive clinical and laboratory dynamics due to the inclusion of D-mannose to the therapy for this type of congenital disorder of glycosylation. No other drugs are mentioned in any of these abstracts.
A 2005 report describes cutaneous findings in congenital disorders of glycosylation, including the hanging fat sign, but offers no treatment data. A 2017 review notes that early diagnosis is important because treatment options are available for some subtypes, but does not specify which subtypes or what those options are. The 2022 review states that molecular genetic testing is the most specific diagnostic test, and that congenital disorders of glycosylation should be considered in any patient with multiorgan involvement.
What is still missing are large-scale clinical trials, given the ultra-rare nature of these diseases, and reliable biomarkers to stratify patients by subtype. The evidence for D-mannose in PMM2-CDG comes from a single case report, not a controlled study. No drug has shown efficacy in a randomised trial for any congenital disorder of glycosylation, and no specific treatment is available for the vast majority of subtypes.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Cutaneous Findings in Congenital Disorders of Glycosylation: The Hanging Fat Sign
AbstractThe congenital disorders of glycosylation are a group of rare metabolic disorders with predominantly neurologic findings. Some variants of this disorder also exhibit cutaneous manifestations. We report a patient with a congenital disorder of glycosylation type Ia, the most common form, with emphasis on the cutaneous findings of this type, and summarize the cutaneous findings in the other forms of the disorder.
Neonatal Presentations of Congenital Disorders of Glycosylation
AbstractCongenital disorders of glycosylation (CDG) are a variable, rapidly expanding group of genetic metabolic disorders. Glycosylation is fundamental to the processing of proteins and lipids, and as such, disorders in these pathways can cause multisystemic effects. Symptoms can be evident as early as the prenatal period and should be suspected in an infant with multisystemic disease. Biochemical screening and confirmatory molecular genetic tests are available; however, their sensitivity is imperfect and some patients are now being diagnosed by whole exome sequencing. Early diagnosis is important, because treatment options are available for some subtypes.
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · 2022 · 3 citations · open access
Congenital disorders of glycosylation
AbstractCongenital disorders of glycosylation are a highly variable, rapidly expanding family of genetic diseases that result from defects in the synthesis of glycans. The vast majority of these monogenic diseases are inherited in an autosomal recessive way, but some types follow an autosomal dominant or X-linked inheritance. The present work aimed to review the state of the art of congenital disorders of glycosylation, including available therapeutic options, and present a simplified diagnostic approach to this group of diseases. Congenital disorders of glycosylation can be classified into four categories: N-linked glycosylation defects, O-linked glycosylation defects, combined glycosylation defects, and glycosphingolipid and glycosylphosphatidylinositol anchor synthesis defects. The phenotype may range from mild to severe, depending on disease severity. Clinical features include dysmorphic features, neurologic, dermatologic, cardiac, endocrine, immunologic, hematologic, gastrointestinal and liver involvement, and skeletal muscle abnormalities. As there is no universal or pathognomonic sign or symptom and no sensitive diagnostic test, it is of foremost importance to keep a high index of suspicion of these diseases. When a congenital disorder of glycosylation is suspected, the first step in screening is to perform serum transferrin isoelectric focusing. Molecular genetic testing is the most specific diagnostic test. Treatment is usually symptomatic, with specific treatment only available for some of these disorders. Since congenital defects of glycosylation may affect any organ at any age and have variable clinical presentation, they should be considered in the differential diagnosis of any patient with multiorgan involvement.
Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) · 2019 · 0 citations · open access
Congenital disorder of glycosilation PMM2-CDG
AbstractCongenital glycosylation disorders represent a group of genetically determined diseases which violate the synthesis and addition of glycans to glycoproteins and glycolipids, and also the synthesis of glycosylphosphatidyl inositol. The most common defects are the defects of protein N-glycosylation. Jaken syndrome, a congenital disorder of PMM2-CDG glycosylation, is the most commonly diagnosed type (about 800 cases worldwide). However, there are only a few descriptions of clinical cases in the Russian literature. The article presents a clinical observation of a child with this type of congenital glycosylation disorder due to a defect in phosphomannomtase 2 (PMM2 gene). The diagnose was based on the combination of clinical, laboratory and instrumental data: a characteristic phenotype, hyperinsulinism, delayed physical and psychomotor development, neurological manifestations, coagulopathy, liver damage, exudative enteropathy, abnormal forms of transferrin, PMM2 gene mutations associated with Jaken’s syndrome. For the first time the authors described positive clinical and laboratory dynamics due to the inclusion of D-mannose to the therapy for this type of congenital glycosylation disorder.
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.
