DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Stickler syndrome type 1 — 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 moduleStickler syndrome type 1 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 stickler syndrome type 1 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
collagen type II alpha 1 chain (COL2A1) — COL2A1 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 p33drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5NIR · 1.74 Å · ligand 3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL (P33). Experimental structure, not a prediction.
What the evidence adds up to
Stickler syndrome type 1 is defined by mutations in COL2A1. Diagnostic criteria based on 25 molecularly confirmed type I patients from six families achieved 100% sensitivity in that group, 98% sensitivity in 47 clinically affected patients from 25 families, and 86% specificity in 18 unaffected patients from seven families, using a nine-point scale that includes molecular or family history data plus ocular, orofacial, auditory, and musculoskeletal findings, with a score of five or more considered diagnostic. In a separate study of six multigeneration families, crossovers between the disease locus and COL2A1 were found in two families, and a weakly positive overall lod score of 0.96 at theta = 0.10 suggested genetic heterogeneity; one family with typical findings had a translocation t(5;17)(q15:q23) segregating with disease in four affected relatives.
In a family with type II Stickler syndrome, 11 patients were identified. Ocular findings included high myopia in 80%, lens subluxation in 70%, exotropia in 50%, and vitreoretinal abnormalities in 80%, with vitreous cavity abnormalities in 50%. On clinical genetic examination, 30% had micrognathia, 50% hearing loss, 40% nasal depression, and 60% high palate. Articular hypermotility and long fingers were present in seven cases, arthropathy in three. The authors noted that diagnosis is difficult due to phenotypic variability and overlap with other genetic syndromes.
A 1963 abstract about angular dependences in multicharged particle production by 75–350 MeV protons appears to be an unrelated paper misattributed to Stickler syndrome. A later report raised the possibility that seizures could occur in Stickler syndrome type 1, suggesting a neurological spectrum in some individuals with heterozygous COL2A1 mutations, but noted that central nervous system involvement is not a typical feature and that the association with epilepsy had not been reported before.
What is still missing: prospective studies with standardised neurological assessment in molecularly confirmed type I cohorts, larger families with linkage data to resolve the heterogeneity suggested by the 1991 crossover findings, and funding for trials that stratify patients by COL2A1 mutation type rather than by clinical diagnosis alone.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2005 · 152 citations · open access
Stickler syndrome: Clinical characteristics and diagnostic criteria
AbstractThe purpose of this study was to establish diagnostic criteria for Stickler syndrome. Ninety patients from 38 families had complete evaluations for possible Stickler syndrome. Molecular confirmation of COL2A1 mutation status (type I Stickler syndrome) was available on 25 patients from six families. In the remaining 65 patients, 47 from 25 families were affected with Stickler syndrome and 18 from seven families were unaffected with Stickler syndrome. A diagnostic nosology based on type I Stickler patients with known COL2A1 mutations was applied to clinically affected and unaffected patients. A diagnostic scale of 9 points evaluated molecular data or family history data and characteristic ocular, orofacial, auditory, and musculoskeletal findings. A score of > or =5 was diagnostic of Stickler syndrome. These criteria demonstrate 100% sensitivity when applied to type I Stickler syndrome patients with known COL2A1 mutations, 98% sensitivity when applied to clinically affected Stickler patients, and 86% specificity when applied to patients unaffected based on clinical and/or molecular analysis. We conclude that diagnostic criteria based on type I Stickler patients with molecularly confirmed COL2A1 mutations appear to be sensitive and specific for the diagnosis of this syndrome and should be helpful to clinicians when making the diagnosis.
American Journal of Medical Genetics · 1991 · 68 citations
Genetic and clinical heterogeneity of Stickler syndrome
AbstractWe have studied 6 multigeneration Stickler syndrome families. Manifestations of the syndrome in the families included myopia, deafness, arthritis, characteristic facial changes with "flat" midface and cleft palate, although not all these were present in all families. COL2A1 has been implicated as a gene which can give rise to Stickler syndrome based on evidence from 2 large families which each showed significant linkage between the disease locus and restriction fragment length polymorphisms for the gene (Francomano CA, Lieberfarb RM, Hirose T, Maumenee IH, Streeten EA, Meyers DA, Pyeritz RE (1987): Genomics 1:293-296; Knowlton RG, Weaver EJ, Struyk AF, Knobloch WH, King RA, Norris K, Shamban A, Uitoo J, Jimenez SA, Prockop DJ (1989): Am J Hum Genet 45:681-688). We have found crossovers between the disease locus and COL2A1 in 2 families with Stickler syndrome. This could be explained by either genetic heterogeneity or the actual mutation being in a closely linked, currently unrecognized gene. We found a weakly positive overall lod score (z = 0.96 at theta = 0.10) suggesting that genetic heterogeneity is a more likely explanation. In one family, with typical findings, a translocation t5;17 (q15:q23) was found to segregate with the disease in 4 affected relatives. In view of the possible heterogeneity, although no crossovers with COL2A1 were seen in this family, either of these breakpoints could be the position of a further disease causing gene.
Arquivos Brasileiros de Oftalmologia · 2006 · 5 citations · open access
Avaliação genética e oftalmológica de pacientes com síndrome de Stickler tipo II
AbstractPURPOSE: To diagnose, evaluate and describe the clinical, genetic and ophthalmic characteristics of a family with type II Stickler syndrome. METHODS: X-rays for bone age, clinical and genetic evaluation were performed in all patients with ocular alterations. The Stickler syndrome diagnosis was established after correlating these examinations. RESULTS: Type II Stickler syndrome was found in 11 patients. The most important ocular findings were: high myopia (80%), lens subluxation (70%), exotropia (50%) and vitreoretinal abnormalities (80%) including vitreous cavity (50%). The clinical genetic examination disclosed that 30% of the patients had micrognathia, 50% hearing loss, 40% nasal depression and 60% high palate. Seven cases had articular hypermotility and long fingers and arthropathy was present in 3 cases. CONCLUSION: Diagnosis of the Stickler syndrome is difficult due to its phenotypic variability and the existence of other genetic syndromes with similar characteristics. Hand and wrist radiographs are of particular importance in the diagnosis of this syndrome.
ANGULAR DEPENDENCES IN MULTICHARGED PARTICLE PRODUCTION BY 75-350 Mev PROTONS
Abstract• Stickler syndrome is a genetically heterogeneous collagenopathy characterized by auditory, ocular, musculoskeletal, and orofacial anomalies. What is New: • Involvement of the nervous central system is not a typical feature of Stickler syndrome and the association with epilepsy has not been reported so far. • This report raises the possibility of a potential occurrence of seizures among the clinical manifestations of Stickler syndrome type 1, suggesting a continuous neurological spectrum in some individuals affected by heterozygous mutations of COL2A1.
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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