DeCure for Congenital disorder of glycosylation, type IIz
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital disorder of glycosylation, type IIz — 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 moduleCongenital disorder of glycosylation, type IIz 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 congenital disorder of glycosylation, type iiz 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
calcium modulating ligand (CAMLG) — CAMLG 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 8CR1 · 3.2 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Congenital disorders of glycosylation type IIz is one of at least 20 such diseases identified by 2004, with new types appearing at roughly one per year since 1980. The 2004 review notes that affected patients have neurologic or multisystem disease, and that disorders of nearly all organs and systems have been reported. The authors recommend that congenital disorders of glycosylation be considered in any child with an unexplained clinical syndrome.
A 2021 review states that despite advances in diagnosis, treatment options remain limited and are often constrained to symptomatic management of disease manifestations. The same review reports that recent years have seen significant advances in treatment and novel therapies aimed at both the causative defect and secondary disease manifestations, but gives no specific survival or response rate data for any therapy.
A 2019 clinical report describes a single child with PMM2-CDG (the most common type, with about 800 cases worldwide) who had a characteristic phenotype, hyperinsulinism, delayed development, neurological manifestations, coagulopathy, liver damage, and exudative enteropathy. The authors claim that including D-mannose in therapy produced positive clinical and laboratory dynamics, but this is a single case, not a controlled trial, and the abstract provides no numerical outcomes or duration of follow-up.
No abstract provides any data on congenital disorder of glycosylation type IIz specifically. What is missing for this ultra-rare subtype is any dedicated clinical trial, any patient stratification by genetic subtype, and any funding for a systematic evaluation of D-mannose or other candidate therapies in a cohort larger than one.
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.
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.
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.
