DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for glycine encephalopathy — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGlycine encephalopathy maps to a 3-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 glycine encephalopathy 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
glycine decarboxylase (GLDC) — GLDC 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 plgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I35 · 2.0 Å · ligand N-GLYCINE-[3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YL-METHANE] (PLG). Experimental structure, not a prediction.
What the evidence adds up to
Glycine encephalopathy, also called nonketotic hyperglycinaemia, is an autosomal recessive disorder caused by a defect in the glycine cleavage enzyme system, leading to glycine accumulation in body fluids. The classic neonatal form presents in the first days of life with hypotonia, lethargy, apnea, and seizures, and usually results in death by one year of age. Two case reports from 2005 describe neonatal glycine encephalopathy accompanied by isolated pes equinovarus deformity. A 2004 review summarises workshop presentations on the disease.
A 2005 study of nine children from a consanguineous Israeli Bedouin kindred with mild glycine encephalopathy found that all were homozygous for a translationally silent GLDC exon 22 mutation that caused missplicing and reduced glycine decarboxylase expression. Clinical features included hypotonia, abnormal movements, convulsions, moderate mental retardation with relative sparing of gross motor function and receptive language, and prominent aggression and irritability. The 4 to 6% of normally spliced GLDC mRNA in these patients may account for their relatively favourable outcome compared with classic disease. An unrelated patient with severe neonatal-onset disease who was haplotypically identical and also homozygous for the same mutation had an unusually favourable outcome.
A 1984 treatment report describes a special diet (without glycine, serine, and with reduced threonine) combined with strychnine nitrate and ursodesoxycholic acid that led to normoglycinaemia in severe nonketotic hyperglycinaemia, but without significant effect on psychomotor development. A 2025 case report describes a neonate with classical glycine encephalopathy and refractory myoclonic seizures whose status epilepticus was successfully treated with a combination of intravenous ketamine, oral dextromethorphan, and sodium benzoate. Seizures resolved and development showed improvement on follow-up. The authors note that intravenous ketamine in the neonatal period has been reported in only two glycine encephalopathy patients previously, and that this is the first report of the triple therapy. A 2015 case report notes that a paradoxical increase in seizure frequency on starting sodium valproate led to the diagnosis of glycine encephalopathy.
What is still missing are controlled trials of any treatment, including the ketamine-dextromethorphan-sodium benzoate combination, in larger numbers of patients. The 1984 diet and strychnine regimen had no effect on development, and the 2025 report is a single case. No therapy has been shown to alter the fundamental developmental outcome in the classic neonatal form, and patient stratification by residual enzyme activity or mutation type may be needed to interpret any future results.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Inherited Metabolic Disease · 2004 · 80 citations
Glycine encephalopathy (nonketotic hyperglycinaemia): Review and update
AbstractAbstract Summary: This article summarizes data and issues covered in the workshop on Glycine Encephalopathy using headings that cover important topics in our present knowledge of this disease. Presenters were: Dr Ada Hamosh (Baltimore); Dr Johan L. K. Van Hove (Leuven); Dr Christine Vianey‐Saban (Lyon); Dr Shigeo Kure (Sendai); Dr A. Ichinohe (Sendai); Jennifer Toone (Vancouver); Dr Stanley Korman (Jerusalem).
Mild glycine encephalopathy (NKH) in a large kindred due to a silent exonic <i>GLDC</i> splice mutation
AbstractBACKGROUND: Classic neonatal-onset glycine encephalopathy (GE) is devastating and life threatening. Milder, later onset variants have been reported but were usually sporadic and incompletely defined. OBJECTIVE: To determine the clinical and biochemical phenotype and molecular basis of mild GE in nine children from a consanguineous Israeli Bedouin kindred. METHODS: Genomic DNA was screened for GLDC, AMT, and GCSH gene mutations. GLDC expression in lymphoblasts was studied by Northern blot and reverse transcriptase PCR analysis. RESULTS: Clinical features included hypotonia, abnormal movements, convulsions, and moderate mental retardation with relative sparing of gross motor function, activities of daily living skills, and receptive language. Aggression and irritability were prominent. CSF-to-plasma glycine ratio was mildly to moderately elevated. All nine patients were homozygous and their parents heterozygous for a novel, translationally silent GLDC exon 22 transversion c.2607C>A. Lymphoblast GLDC mRNA levels were considerably reduced. Three aberrantly spliced cDNA species were identified: exon 22 and exon 22 to 23 skipping, and insertion of an 87-base pair cryptic exon. Homozygosity for c.2607C>A was also identified in an unrelated but haplotypically identical patient with an unusually favorable outcome despite severe neonatal-onset GE. Mutation analysis enabled prenatal diagnosis of three unaffected and one affected pregnancies. CONCLUSIONS: The mutation in this kindred led to missplicing and reduced GLDC (glycine decarboxylase) expression. The 4 to 6% of normally spliced GLDC mRNA in the patients may account for their relatively favorable clinical outcome compared with patients with classic glycine encephalopathy.
Journal of Pediatric Neurosciences · 2015 · 10 citations
A rare case of glycine encephalopathy unveiled by valproate therapy
AbstractGlycine encephalopathy (GE) or nonketotic hyperglycinemia is an autosomal recessive disorder due to a primary defect in glycine cleavage enzyme system. It is characterized by elevated levels of glycine in plasma and cerebrospinal fluid usually presenting with seizures, hypotonia, and developmental delay. In our case, paradoxical increase in seizure frequency on starting sodium valproate led us to diagnose GE.
Journal of Inherited Metabolic Disease · 1984 · 1 citations
A treatment of non‐ketotic hyperglycinaemia
AbstractThe treatment comprising a special diet (without glycine, serine, and with a reduced amount of threonine), strychnine nitrate and ursodesoxycholic acid (UDCA) led to normoglycinaemia in this form of severe non-ketotic glycine encephalopathy. Diet and treatment were well tolerated but without significant effect upon psychomotor development. This treatment should be more effective if administered before irreversible brain damage occurs, particularly in moderate and chronic forms of NKH.
Seizure control in glycine encephalopathy using the Ketamine-Dextromethorphan-Sodium benzoate triple therapy
AbstractNeonatal glycine encephalopathy is a rare genetic neurometabolic disorder secondary to glycine cleavage system deficiency. Patients typically present with early-onset intractable seizures, status epilepticus and encephalopathy. Seizures control remains challenging in view of their refractoriness to standard anti-seizure medications. Sodium benzoate is commonly used to control the elevated glycine level. Oral anti-NMDA receptor antagonists, ketamine and dextromethorphan, have been used in various combinations in the treatment of this complex disorder. In this report, we present a neonatal case of classical glycine encephalopathy with hypotonia and refractory myoclonic seizures. The status epilepticus was successfully treated using a combination of intravenous ketamine, oral dextromethorphan and sodium benzoate. Seizures resolved and the patient's development showed improvement on follow-up. The intravenous form of ketamine in the neonatal period is rarely used, and it has been reported in only two glycine encephalopathy patients in the literature. This is the first report in the literature of the efficacy of intravenous ketamine using the above triple therapy. This intervention might have implications on the management of neonatal intractable seizures in glycine encephalopathy, which might improve the outcome of this devastating disorder.
Two Cases of Glycine Encephalopathy Accompanied by Pes Equinovarus
AbstractGlycine encephalopathy is a rare autosomal recessive metabolic disease characterized by glycine accumulation in body fluids owing to a defect in the glycine cleavage system. There are several forms of glycine encephalopathy. In the classic or neonatal form, symptoms usually develop as neurologic symptoms in the first few days of life. It characteristically presents with hypotonia, lethargy, apnea, and seizures and usually results in death by 1 year of age. In this report, we present two cases of neonatal glycine encephalopathy accompanied by isolated pes equinovarus deformity. ( J Child Neurol 2005;20:533-535).
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.
