DeCure for MGAT2-congenital disorder of glycosylation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for MGAT2-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 moduleMGAT2-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 mgat2-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
MAGT1 mutations cause a congenital disorder of glycosylation (CDG) that presents with intellectual and developmental disability, but the same gene was previously linked to a primary immunodeficiency called XMEN, characterised by chronic EBV infections attributed to a magnesium homeostasis defect. In a 2019 study, two patients with defective serum transferrin glycosylation and MAGT1 mutations were compared to an XMEN patient. All three had an N-glycosylation defect, shown by dysfunctional posttranslational glycosylation carried out by the STT3B complex on substrates such as GLUT1 and SHBG. MAGT1 deficiency was associated with enhanced expression of its homolog TUSC3, suggesting a compensatory mechanism. The authors concluded that MAGT1-CDG is a disorder with two different clinical phenotypes both caused by defects in glycosylation.
A 2024 overview of CDG treatments states that available options are still quite limited, with most management addressing symptoms rather than the underlying cause. It notes that recent years have brought remarkable advances in treatment approaches for some CDG, with innovative therapies targeting both root cause and manifestations transitioning from research to practical application. The paper aims to provide a detailed overview of these developments for ultra-rare diseases.
A 2019 Russian clinical report describes a child with PMM2-CDG (Jacken syndrome), the most common CDG type with about 800 cases worldwide. The diagnosis was based on characteristic phenotype, hyperinsulinism, delayed development, neurological manifestations, coagulopathy, liver damage, exudative enteropathy, abnormal transferrin forms, and PMM2 gene mutations. The authors reported positive clinical and laboratory dynamics after including D-mannose in therapy for this specific type.
What is still missing: no controlled trials of D-mannose for PMM2-CDG are described; no treatment data for MAGT1-CDG are given beyond the observation of a compensatory mechanism; the 2024 overview does not specify which CDG types the new therapies apply to or provide response rates or survival numbers; patient stratification by mutation type or clinical phenotype remains unaddressed; funding for trials in these ultra-rare diseases is not mentioned.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Proceedings of the National Academy of Sciences · 2019 · 92 citations · open access
Mutations in <i>MAGT1</i> lead to a glycosylation disorder with a variable phenotype
AbstractCongenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. We identified two patients with defective serum transferrin glycosylation and mutations in the MAGT1 gene. These patients present with a phenotype that is mainly characterized by intellectual and developmental disability. MAGT1 has been described to be a subunit of the oligosaccharyltransferase (OST) complex and more specifically of the STT3B complex. However, it was also claimed that MAGT1 is a magnesium (Mg 2+ ) transporter. So far, patients with mutations in MAGT1 were linked to a primary immunodeficiency, characterized by chronic EBV infections attributed to a Mg 2+ homeostasis defect (XMEN). We compared the clinical and cellular phenotype of our two patients to that of an XMEN patient that we recently identified. All three patients have an N -glycosylation defect, as was shown by the study of different substrates, such as GLUT1 and SHBG, demonstrating that the posttranslational glycosylation carried out by the STT3B complex is dysfunctional in all three patients. Moreover, MAGT1 deficiency is associated with an enhanced expression of TUSC3, the homolog protein of MAGT1, pointing toward a compensatory mechanism. Hence, we delineate MAGT1-CDG as a disorder associated with two different clinical phenotypes caused by defects in glycosylation.
Molecular Genetics and Metabolism · 2024 · 12 citations · open access
Treatment of congenital disorders of glycosylation: An overview
AbstractWhile the identification and diagnosis of congenital disorders of glycosylation (CDG) have rapidly progressed, the available treatment options are still quite limited. Mostly, we are only able to manage the disease symptoms rather than to address the underlying cause. However, recent years have brought about remarkable advances in treatment approaches for some CDG. Innovative therapies, targeting both the root cause and resulting manifestations, have transitioned from the research stage to practical application. The present paper aims to provide a detailed overview of these exciting developments and the rising concepts that are used to treat these ultra-rare diseases.
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.
