DeCure for ALG1-congenital disorder of glycosylation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for ALG1-congenital disorder of glycosylation — 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 moduleALG1-congenital disorder of glycosylation 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 alg1-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
eukaryotic elongation factor 2 lysine methyltransferase (EEF2KMT) — EEF2KMT 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 sahdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8FZB · 3.35 Å · ligand S-ADENOSYL-L-HOMOCYSTEINE (SAH). Experimental structure, not a prediction.
What the evidence adds up to
In 2004, the total number of known congenital disorders of glycosylation stood at 20, with roughly one new disease identified per year since 1980. The review noted that disorders of nearly all organs and systems had been reported and recommended that CDG be considered in any child with an unexplained clinical syndrome. A 2017 retrospective study of 27 Saudi patients from 13 families found no ALG1-CDG cases; the subtypes identified were ALG9-CDG (8 patients), ALG3-CDG (7 patients), COG6-CDG (7 patients), MGAT2-CDG (3 patients), SLC35A2-CDG (1 patient), and PMM2-CDG (1 patient). The combined carrier frequency of founder mutations in that population was 11.5 per 10,000, translating to a minimum disease burden of 14 patients per 1,000,000.
A 2021 report on ALG3-CDG described 10 new individuals with 11 novel variants, bringing the total reported ALG3-CDG patients to 40. The expanded phenotype included endocrine abnormalities, neural tube defects, mild aortic root dilatation, immunodeficiency, and renal anomalies, in addition to the previously known severe neurological involvement, ocular anomalies, dysmorphic features, skeletal anomalies, and feeding difficulties. N-glycan analyses showed combined deficiencies of hybrid glycans and glycan extension beyond Man5GlcNAc2, a pattern described as unique to ALG3-CDG. A 2019 report on ALG11-CDG described two unrelated patients with novel mutations who had severe psychomotor disabilities and epilepsy; one of them had a normal transferrin glycosylation profile, a feature not previously reported in that subtype.
No abstract in this set provides any treatment data, clinical trial results, or survival statistics for ALG1-CDG. The 2017 neonatal review states that treatment options are available for some CDG subtypes but does not specify which ones. What is missing for ALG1-CDG specifically is any published evidence of a tested therapy, any patient cohort large enough to measure response, and any biomarker or stratification strategy that could guide a trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
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.
Journal of Inherited Metabolic Disease · 2021 · 21 citations · open access
Expanding the phenotype, genotype and biochemical knowledge of <scp>ALG3‐CDG</scp>
AbstractAbstract Congenital disorders of glycosylation (CDGs) are a continuously expanding group of monogenic disorders of glycoprotein and glycolipid biosynthesis that cause multisystem diseases. Individuals with ALG3‐CDG frequently exhibit severe neurological involvement (epilepsy, microcephaly, and hypotonia), ocular anomalies, dysmorphic features, skeletal anomalies, and feeding difficulties. We present 10 unreported individuals diagnosed with ALG3‐CDG based on molecular and biochemical testing with 11 novel variants in ALG3 , bringing the total to 40 reported individuals. In addition to the typical multisystem disease seen in ALG3‐CDG, we expand the symptomatology of ALG3‐CDG to now include endocrine abnormalities, neural tube defects, mild aortic root dilatation, immunodeficiency, and renal anomalies. N‐glycan analyses of these individuals showed combined deficiencies of hybrid glycans and glycan extension beyond Man 5 GlcNAc 2 consistent with their truncated lipid‐linked precursor oligosaccharides. This spectrum of N‐glycan changes is unique to ALG3‐CDG. These expanded features of ALG3‐CDG facilitate diagnosis and suggest that optimal management should include baseline endocrine, renal, cardiac, and immunological evaluation at the time of diagnosis and with ongoing monitoring.
American Journal of Medical Genetics Part A · 2019 · 15 citations · open access
ALG11‐CDG syndrome: Expanding the phenotype
AbstractALG11-Congenital Disorder of Glycosylation (ALG11-CDG, also known as congenital disorder of glycosylation type Ip) is an inherited inborn error of metabolism due to abnormal protein and lipid glycosylation. We describe two unrelated patients with ALG11-CDG due to novel mutations, review the literature of previously described affected individuals, and further expand the clinical phenotype. Both affected individuals reported here had severe psychomotor disabilities and epilepsy. Their fibroblasts synthesized truncated precursor glycan structures, consistent with ALG11-CDG, while also showing hypoglycosylation of a novel biomarker, GP130. Surprisingly, one patient presented with normal transferrin glycosylation profile, a feature that has not been reported previously in patients with ALG11-CDG. Together, our data expand the clinical and mutational spectrum of ALG11-CDG.
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.
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.
