DeCure for Gerstmann-Straussler-Scheinker syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Gerstmann-Straussler-Scheinker syndrome — 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 moduleGerstmann-Straussler-Scheinker syndrome 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 gerstmann-straussler-scheinker syndrome 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
prion protein (Kanno blood group) (PRNP) — PRNP 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 6LNI · 2.702 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Two patients from separate families with Gerstmann-Sträussler-Scheinker disease carried the P102L mutation in the prion protein gene, with methionine at codon 129. The clinical diagnosis was confirmed by neuropathological examination in both. This mutation had been reported in at least 30 other families before 1995.
A 61-year-old woman with no family history of neurodegenerative disease died one month after minor elective surgery, having developed rapidly progressive dementia, altered behaviour, and cerebellar ataxia. Brain autopsy showed neuronal loss, sparse spongiform change, and diffuse multicentric amyloid plaques that were selectively immunoreactive for prion protein. Tau-immunoreactive neurofibrillary tangles and neuritic threads were present in the cerebral cortex. PRNP sequencing revealed a valine-to-glycine mutation at codon 176, with valine homozygosity at codon 129. Western blot of frozen brain tissue showed a non-classic protease-resistant prion protein banding pattern with a prominent approximately 8-kDa fragment. This was a novel mutation at the time.
A separate 61-year-old woman with GSS underwent two surgeries for large and small bowel obstruction. The report describes precautions taken with disposable devices during endotracheal intubation and the surgical procedure, but provides no data on disease progression, survival, or any therapeutic intervention.
No treatment, no drug, and no measurable clinical outcome from any intervention is reported in any of these abstracts. What remains missing is any trial of a candidate therapy, any systematic collection of longitudinal clinical data across GSS mutations, and any patient stratification by genotype or codon 129 status that could support a future trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 1995 · 39 citations
Gerstmann‐Straussler‐Scheinker disease with mutation at codon 102 and methionine at codon 129 of <i>PRNP</i> in previously unreported patients
AbstractWe present two patients with Gerstmann-Sträussler-Scheinker disease (GSS), one from a previously undescribed kindred and one from the Canadian branch of a previously reported British kindred. In both patients, GSS is caused by a substitution of thymine for cytosine at codon 102 of the prion protein gene (PRNP). In each patient, we confirmed the clinical diagnosis by neuropathologic examination. The mutation, causing a substitution of leucine for proline at residue 102 (P102L) of the prion protein, has been previously reported in at least 30 other families. In the patients described here, the mutation was in coupling with methionine at PRNP codon 129.
JAMA Neurology · 2013 · 20 citations · open access
Unusual Clinical and Molecular-Pathological Profile of Gerstmann-Sträussler-Scheinker Disease Associated With a Novel<i>PRNP</i>Mutation (V176G)
AbstractIMPORTANCE: Here we describe the unusual clinical and molecular-neuropathological profile of a case of Gerstmann-Sträussler-Scheinker disease associated with a novel prion protein (PRNP) gene mutation. OBSERVATIONS: This case report from the Australian National Creutzfeldt-Jakob Disease Registry concerns a 61-year-old British-born woman with no history of neurodegenerative disorder in first-degree relatives. Rapidly progressive dementia, altered behavior, and cerebellar ataxia dominated the clinical picture in the period immediately following minor elective surgery, with death 1 month later in an akinetic-mute state. Brain histopathological examination revealed neuronal loss, scant foci of spongiform change, and diffuse multicentric amyloid plaques, selectively immunoreactive for prion protein, within the cerebral and cerebellar cortices and deep gray matter. Tau immune-reactive neurofibrillary tangles and neuritic threads were present in the cerebral cortex. PRNP sequencing demonstrated a valine to glycine mutation at codon 176, with valine homozygosity at polymorphic codon 129. Western-blot analysis of frozen brain tissue displayed a nonclassic protease-resistant prion protein banding pattern, with a prominent approximately 8-kDa protease-resistant fragment. CONCLUSIONS AND RELEVANCE: Reported is a proband with a novel PRNP mutation associated with neuropathologically confirmed Gerstmann-Sträussler-Scheinker disease displaying a somewhat unusual constellation of clinicopathological features, which overall subserve to further broaden an already diverse phenotypic spectrum.
Intractable & Rare Diseases Research · 2020 · 0 citations · open access
A rare challenge in general surgery: double surgical procedure for large and small bowel obstruction in a patient with Gerstmann-Sträussler-Scheinker syndrome
AbstractGerstmann-Sträussler-Scheinker syndrome (GSS) is a rare, infectious syndrome related to a mutation in the prion protein gene. Described here are the challenges posed by surgery for a patient with GSS. A 61-yr-old woman with GSS was admitted to this department and underwent surgery twice for large and small bowel obstruction. This is the first report of two major surgical procedures in a patient with GSS. Experiences with this case and precautions when using a disposable device during endotracheal intubation and a surgical procedure to manage a patient with GSS are described.
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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