DeCure for SLC35A1-congenital disorder of glycosylation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for SLC35A1-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 moduleSLC35A1-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 slc35a1-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.
What the evidence adds up to
Only five types of congenital disorders of glycosylation related to impaired fucosylation have been described: FUT8-CDG, FCSK-CDG, POFUT1-CDG, SLC35C1-CDG, and GFUS-CDG. A 2021 review summarised the clinical findings of all 25 known patients with those defects and discussed the efficacy of fucose therapy approaches within the different defects. No abstract in this set reports any fucose therapy trial or outcome for SLC35A1-CDG specifically.
Treatment options for congenital disorders of glycosylation in general remain limited and are often constrained to symptomatic management of disease manifestations. A 2024 overview states that while identification and diagnosis have rapidly progressed, available treatments are still quite limited, and mostly we are only able to manage symptoms rather than address the underlying cause. The same overview notes that innovative therapies targeting both the root cause and resulting manifestations have transitioned from research to practical application for some CDG, but does not name SLC35A1-CDG among them.
A 2018 case report describes a 27-month-old girl with a mosaic missense variant in SLC35A2, a different gene that encodes a UDP-galactose transporter. That patient had developmental delay, central hypotonia, cerebral atrophy, and failure to thrive with growth retardation. The report notes that transferrin isoform analysis, the most common test for congenital disorders of glycosylation, did not identify this patient. No abstract in this set describes a single patient with SLC35A1-CDG, nor any treatment tested for that specific defect.
What is still missing for SLC35A1-CDG is any published clinical trial, any reported attempt at substrate replacement or small-molecule therapy, and any patient cohort large enough to test a candidate treatment. The fundamental gaps are money for preclinical work, a trial design that can cope with an ultra-rare population, and a method to stratify patients by residual enzyme activity or glycosylation status.
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.
Journal of Inherited Metabolic Disease · 2021 · 27 citations · open access
Congenital disorders of glycosylation with defective fucosylation
AbstractFucosylation is essential for intercellular and intracellular recognition, cell-cell interaction, fertilization, and inflammatory processes. Only five types of congenital disorders of glycosylation (CDG) related to an impaired fucosylation have been described to date: FUT8-CDG, FCSK-CDG, POFUT1-CDG SLC35C1-CDG, and the only recently described GFUS-CDG. This review summarizes the clinical findings of all hitherto known 25 patients affected with those defects with regard to their pathophysiology and genotype. In addition, we describe five new patients with novel variants in the SLC35C1 gene. Furthermore, we discuss the efficacy of fucose therapy approaches within the different defects.
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.
Mosaicism of the UDP-Galactose transporter SLC35A2 in a female causing a congenital disorder of glycosylation: a case report
AbstractAbstract Background Congenital disorders of glycosylation are rare conditions caused by genetic defects in glycan synthesis, processing or transport. Most congenital disorders of glycosylation involve defects in the formation or transfer of the lipid-linked oligosaccharide precursor of N-linked glycans. SLC35A2-CDG (previously CDG-IIm) is caused by hemizygous or heterozygous mutations in the X-linked gene SLC35A2 that encodes a UDP-galactose transporter. To date there have only been 10 reported patients with SLC35A2 mutations. Importantly, the patient presented here was not identified in infancy by transferrin isoform analysis, the most common testing to identify patients with a congenital disorder of glycosylation. Case presentation A 27Â month old girl with developmental delay, central hypotonia, cerebral atrophy, and failure to thrive with growth retardation was identified by whole exome sequencing to have a mosaic missense variant in SLC35A2 (c.991Gâ >â A). This particular variant has been previously reported in a male as a mutation. Comparison of all clinical findings and new information on growth pattern, growth hormone testing and neurodevelopmental evaluation are detailed on the patient presented. Conclusion This patient report increases the clinical and scientific knowledge of SLC35A2-CDG, a rare condition. New information on reduced growth, growth hormone sufficiency, lack of seizures, and neurodevelopmental status are presented. This new information will be helpful to clinicians caring for individuals with SLC35A2-CDG. This report also alerts clinicians that transferrin isoform measurements do not identify all patients with congenital disorders of glycosylation.
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.
