DeCure for Glycogen storage disease due to glucose-6-phosphatase deficiency
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for Glycogen storage disease due to glucose-6-phosphatase deficiency — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGlycogen storage disease due to glucose-6-phosphatase deficiency maps to a 5-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 glycogen storage disease due to glucose-6-phosphatase deficiency 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
argininosuccinate synthase 1 (ASS1) — ASS1 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 aspdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2NZ2 · 2.4 Å · ligand ASPARTIC ACID (ASP). Experimental structure, not a prediction.
What the evidence adds up to
Glycogen storage disease type 1a is caused by deficiency of D-glucose-6-phosphatase, the key enzyme in glucose homeostasis. In 1993, researchers reported the molecular and biochemical characterisation of the human G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase. Several mutations in the G6Pase gene of affected individuals that completely inactivate the enzyme were identified. The authors stated that these results established the molecular basis of the disease and opened the way for future gene therapy, but no gene therapy results were presented in that abstract.
A 1992 report described 10 patients first diagnosed with glycogen storage disease in adult life. Five had type 1a, one had type 1c, two had type IX, and two had previously unreported abnormalities of the hepatic glucose-6-phosphatase system. One of those two had an inhibitor of liver glucose-6-phosphatase (pseudo-1b glycogen storage disease), and the other had abnormal glucose-6-phosphatase activity and microsomal pyrophosphate transport. The authors suggested a glucagon test as a useful screening procedure and stated that glycogen storage disease should be considered in adults with symptoms suggesting hypoglycaemia.
A 1986 review noted that the incidence of glycogen storage diseases is low, at or below 1 per 100,000 live births for each disorder. The same review credited the Coris with demonstrating the first hepatic enzyme deficiency in humans, that of glucose-6-phosphatase, three decades earlier. A 2020 entry from the Orphanet database, citing a 1999 source, defined glycogen storage disease type 1b as a type of glycogenosis due to G6P deficiency, but provided no new clinical or experimental data.
No controlled trials of any drug for this condition were reported in these abstracts. What is still missing is any evidence from a prospective clinical trial, any validated surrogate endpoint for long-term outcomes, and any patient stratification beyond the broad enzyme-deficiency categories.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science · 1993 · 386 citations
Mutations in the Glucose-6-Phosphatase Gene that Cause Glycogen Storage Disease Type 1a
AbstractGlycogen storage disease (GSD) type 1a is caused by the deficiency of D-glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Despite both a high incidence and morbidity, the molecular mechanisms underlying this deficiency have eluded characterization. In the present study, the molecular and biochemical characterization of the human G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase, are reported. Several mutations in the G6Pase gene of affected individuals that completely inactivate the enzyme have been identified. These results establish the molecular basis of this disease and open the way for future gene therapy.
AbstractGlycogen storage diseases are usually identified in childhood. We present the clinical, biochemical and histological features of 10 patients first diagnosed in adult life. Five had glycogen storage disease type 1a, one type 1c, two type IX, and in two patients there were previously unreported abnormalities of hepatic glucose-6-phosphatase system activity. Of the latter, one patient had an inhibitor of liver glucose-6-phosphatase (pseudo-1b glycogen storage disease) the other having abnormal glucose-6-phosphatase activity and microsomal pyrophosphate transport. A glucagon test is suggested as a useful screening procedure. Glycogen storage disease should be considered in adults with symptoms suggesting hypoglycaemia.
New England Journal of Medicine · 1986 · 9 citations
Nutritional Goals in Glycogen Storage Disease
AbstractThree decades ago the pioneering work of Cori and Cori demonstrated the first hepatic enzyme deficiency in humans, that of glucose-6-phosphatase, and elucidated the biochemical bases of several glycogen storage diseases.1 In the ensuing years, inherited abnormalities of most of the enzymes of glycogen metabolism have been correlated with specific clinical entities. Although the incidence of the glycogen storage diseases is low (≤1 per 100,000 live births for each disorder), an understanding of these disorders has had an important influence on our knowledge of normal metabolism and the biochemical adaptations available to the human organism. Glucose-6-phosphatase deficiency (glycogen storage disease . . .
American journal of diseases of children · 1985 · 9 citations
X-linked Glycogen Storage Disease
AbstractSeven male members of one family had a form of glycogen storage disease that was inherited in an X-linked recessive pattern. The clinical manifestations included hepatomegaly, delay in growth and sexual maturation, muscular weakness in childhood, and gouty arthritis. The cause of the glycogen accumulation did not appear to be a deficiency of glucose 6-phosphatase, debrancher enzyme, phosphorylase, or phosphorylase kinase. Prognosis appeared to be good although there was significant disability during childhood.
AbstractWe have described a 20-month-old child with type IB glycogen storage disease, based on clinical and biochemical manifestations. Functional testing data were similar to those found in glucose-6-phosphatase deficiency, but in vitro studies showed normal hepatic glucose-6-phosphatase activity. Disruption of membranes with deoxycholic acid was followed by an increase in enzyme activity compared to a control liver tissue, suggesting "latency" of enzyme. We suggest that this patient had glycogen storage type IB and that this disorder may represent a specific glucose-6-phosphate transport defect.
Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib
AbstractOpe n Pe e r Re v ie w on Qe ios Ope n Pe e r Re v ie w on Qe ios Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib INSERM Source INSERM.(1999).Orphanet: an online rare disease and orphan drug data base.Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib.ORPHA:79259Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type b, or glycogen storage disease (GSD) type 1b, is a type of glycogenosis due to G6P deficiency (see this term).
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.
