DeCure for ALG2-congenital disorder of glycosylation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for ALG2-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 moduleALG2-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 alg2-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
ATPase H+ transporting accessory protein 1 (ATP6AP1) — ATP6AP1 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 methyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6WLW · 3.0 Å · ligand tri(methyl)-[2-[[(2~{R})-2-[(~{Z})-octadec-9-enoyl]oxy-3-[(~{E})-1-oxidanylideneoctadec-9-enoxy]propoxy]-oxidanyl-phosphoryl]oxyethyl]azanium (WSS). Experimental structure, not a prediction.
What the evidence adds up to
No drug treatment is described in these abstracts for ALG2-CDG specifically. The 2021 review states that for congenital disorders of glycosylation generally, treatment options remain limited and are often constrained to symptomatic management of disease manifestations, though it notes recent advances in therapies aimed at the causative defect and secondary manifestations have been transferred from bench to bedside. No concrete numbers, survival data, or response rates are given for any drug.
The 2019 paper describes ALG11-CDG, a related disorder, in two patients with severe psychomotor disabilities and epilepsy. One patient had a normal transferrin glycosylation profile, a feature not previously reported. The 2025 paper describes three ALG1-CDG cases from Iran with a novel homozygous variant; all had seizures at a young age, developmental delays, speech and learning disabilities, and walking problems. The youngest case gained the ability to walk through occupational therapy. All three survived to childhood and adulthood, which the authors interpret as a mild phenotype. No drug intervention is reported in either of these case series.
No abstract in this set addresses ALG2-CDG directly. The 2021 review covers the entire CDG field but provides no drug-specific data for ALG2-CDG. What is missing is any clinical trial, any tested compound, any patient stratification for ALG2-CDG, and any funding directed at this specific subtype. The only interventions mentioned are symptomatic management and occupational therapy.
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.
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.
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.
Egyptian Journal of Medical Human Genetics · 2025 · 1 citations · open access
ALG1-congenital disorder of glycosylation: report of clinical and genetic features of three new cases and review of literature
AbstractAbstract Background The ALG1-congenital disorder of glycosylation condition is a rare autosomal recessive disorder with approximately 80 patients reported worldwide up to now. This disorder is caused by a deficiency of β1,4 mannosyltransferase due to the pathogenic variants within the ALG1 gene which leads to impaired protein glycosylation. This disorder usually causes multiorgan damage. This is the first report of ALG1-CDG cases from Iran who are bearing a novel variant in a homozygote state. Case presentation The clinical and molecular features of three cases have been described. All three cases in this study had experienced seizures at a young age and had developmental delays. They were suffering from speech and learning disabilities, and in one case, cerebral atrophy was also present. Although they all had walking problems, the youngest case gained the ability to walk by occupational therapy. Additionally, they all survived to childhood and adulthood which indicates a mild phenotype. Despite several years of delayed diagnosis, a novel variant p.Leu375Gln was identified in the cases in homozygous form through whole exome sequencing, which ultimately established a diagnosis. The pathogenic effect of the novel variant was assessed computationally. It has been evaluated using prediction tools including SIFT, Poly-Phen2, and Mutation taster. The protein homology modeling was performed, and the variant effect on hydrogen bonds and protein stability was assessed. Conclusion The findings of this study expand our knowledge of clinical and genetic features of ALG1-CDG and present the significant role of next-generation sequencing technologies in the diagnosis of rare disorders.
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.
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