DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Stickler syndrome type 2 — 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 2 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 2 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 I alpha 1 chain (COL1A1) — COL1A1 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 eladrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7E7B · 2.6 Å · ligand Elaidic acid (ELA). Experimental structure, not a prediction.
What the evidence adds up to
The 2005 diagnostic criteria paper studied 90 patients from 38 families, with molecular confirmation of COL2A1 mutation available for 25 patients from six families. A nine-point diagnostic scale gave 100% sensitivity in type I patients with known COL2A1 mutations, 98% sensitivity in clinically affected patients, and 86% specificity in patients judged unaffected by clinical or molecular analysis. A score of five or more was considered diagnostic. The 1995 paper identified a single base deletion in exon 50 of COL2A1, causing a premature stop codon in exon 51 within the globular C-propeptide region, in all affected members of a three-generation family. The authors concluded that premature stop codons are a common cause of Stickler syndrome and that a truncated C-propeptide of at least 84 amino acids is inadequate for a functional gene product.
The 2020 review states that Stickler syndrome is caused by mutations in one of six collagen genes: COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, or COL9A3. The 2014 case report describes a newborn with a family history and a COL2A1 gene mutation, emphasising early detection and treatment. The 2025 cross-sectional questionnaire study included 24 adults with a verified diagnosis. Ninety-two percent reported chronic pain, along with fatigue, anxiety symptoms, and reduced quality of life. Participants still reported education, employment, and family life. The scoping review component found limited existing research on quality of life in Stickler syndrome.
No drug treatment or repurposing candidate is mentioned in any of these abstracts. There is no data on any pharmacological intervention for Stickler syndrome type 2 or any other subtype. What is missing is any clinical trial testing a drug, any preclinical model of drug effect, any funding for such work, and any stratification of patients by genotype beyond the broad gene-level classification. The 2025 study notes that further studies are needed to develop evidence-based practice for this group, but no specific trial design or compound is proposed.
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.
AbstractBACKGROUND: All of the mutations in the type II procollagen (COL2A1) gene that have been identified in families affected with Stickler syndrome have been located primarily in the triple helical region of the gene. We report what we believe is the first premature stop codon in the globular C-propeptide region encoded by the COL2A1 gene, in a family affected with Stickler syndrome. DESIGN: Genomic DNA from affected and unaffected family members of this three-generation family was amplified using the polymerase chain reaction. The polymerase chain reaction products were directly sequenced for DNA analysis. RESULTS: Direct sequencing showed a single base deletion in exon 50, resulting in a premature stop codon in exon 51 in the globular C-propeptide of COL2A1 gene in all affected members. CONCLUSIONS: These results implicate premature stop codons as a common cause of Stickler syndrome. The location of this premature stop codon in the far end of the nonhelical 3' end of the gene indicates that a truncated C-propeptide of at least 84 amino acid residues is inadequate for the functional gene product.
Disability and Rehabilitation · 2025 · 1 citations · open access
Psychosocial aspects, chronic pain, fatigue and quality of life in individuals with Stickler syndrome: a scoping review and a cross-sectional questionnaire study
AbstractPURPOSE: Stickler syndrome is a rare, hereditary connective tissue disorder characterized by visual, auditory, and musculoskeletal complications. Research on quality of life remains limited. This study aimed to: (i) explore existing literature on psychosocial aspects, pain, fatigue, and quality of life in individuals with Stickler syndrome, (ii) describe the impact of health complaints on daily living, contacts with healthcare- and social service systems and quality of life in a cohort of adults with Stickler syndrome. METHODS: A combination of a systematic scoping review and a cross-sectional questionnaire study was utilized. The questionnaire included questions on demographics and health complaints, and several validated instruments: PROMIS-57, Satisfaction with Life Scale and LiSat-11. Only patients with a verified diagnosis were included. RESULTS: = 24), 92% reported chronic pain, along with fatigue, anxiety symptoms, and reduced quality of life. Still, participants reported education, employment, and family life. CONCLUSION: Individuals with Stickler syndrome experience health challenges affecting various aspects of life. Further studies are needed to develop evidence-based practice for this group.
A Case of Familial Stickler Syndrome in a Newborn with<i>COL2A1</i>Gene Mutation
AbstractStickler syndrome is a progressive, hereditary disorder of connective tissue caused by mutations in different collagen genes. It is characterized by distinctive ocular, auditory, skeletal and oro-facial abnormalities and associated with long-term respiratory, nutritional, and developmental difficulties. Therefore, early detection and early treatment of Stickler syndrome is very important. We reported a case of Stickler syndrome in a newborn with family history and COL2A1 gene mutation.
Archives of Immunology and Allergy · 2020 · 0 citations · open access
The Role of Genetic Mutations in Genes COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, COL9A3 in Stickler Syndrome
AbstractStickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems.These signs and symptoms vary widely among affected individuals.Stickler syndrome is caused by genetic changes (mutations or pathogenic variants) in one of six genes: COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, or COL9A3.These genes are all responsible for providing instructions to the body to produce collagen.
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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