DeCure for Fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement — 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 moduleFibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement 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 fibrosis of extraocular muscles, congenital, 3a, with or without extraocular involvement 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
tubulin beta 3 class III (TUBB3) — TUBB3 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 gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6S8L · 1.801 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
A 2009 case report describes a 7-year-old girl with congenital fibrosis of the extraocular muscles who showed either synergistic divergence or adduction during attempted gaze. Her corrected visual acuities were 20/50 in both eyes, she had 12 prism dioptres of exotropia at distance and near in primary position, levator function was 0 mm with a marginal reflex distance of -1 in both eyes, and upgaze and downgaze were limited. Magnetic resonance imaging showed the left abducens nerve absent and both oculomotor nerves severely hypoplastic; the medial and superior recti of both eyes were atrophic. The authors note this pattern of alternating synergistic divergence or adduction had not been documented before.
A 2012 study of a Chinese family with congenital fibrosis of extraocular muscles type 2 identified a heterozygous mutation in the PHOX2A gene: 227T to G (N76K) in exon 2. Linkage analysis found the mutation at 11q13 between markers D11S4151 and D11S1320. The mutation was absent in unaffected family members and 100 normal controls. The authors conclude this mutation is responsible for the condition in that family.
A 2022 retrospective case report describes a patient with infantile esotropia who carried a heterozygous TUBB3 variant c.904 G > A (p.A302T) known to cause type 3 congenital fibrosis of the extraocular muscles (CFEOM3). Family members also presented with CFEOM3 manifestations. The authors note that CFEOM3 clinical features are diverse, ranging from mild ptosis and limited eye movement to severe motility problems and central nervous system abnormalities, and recommend considering CFEOM3 when congenital extraocular muscle movement abnormality and positive family history are present.
A 2014 case report describes a child with unilateral restrictive ophthalmoplegia affecting the right eye, comprising unilateral fibrosis, blepharoptosis and enophthalmos without the intraorbital mass typical of congenital orbital fibrosis, which was once considered a rare form of congenital fibrosis of extraocular muscles. The report reviews the history and clinical features of the condition but provides no new genetic or treatment data. What remains missing is any systematic trial of a drug for any form of congenital fibrosis of extraocular muscles, any quantitative natural history data from a cohort large enough to stratify by genotype, and any funding for such work.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Optometry and Vision Science · 2009 · 6 citations
Variable Synergistic Divergence
AbstractPURPOSE: To report a patient with congenital fibrosis of the extraocular muscles showing either synergistic divergence or adduction. CASE REPORT: A 7-year-old girl presented with complaints of abnormal eye movement since early childhood. A detailed ophthalmologic examination was performed. On ophthalmologic evaluation, her corrected visual acuities were 20/50 OU. She had 12 prism diopters of exotropia at distance and near in the primary position. During attempted right gaze, OU abducted. During attempted left gaze, the right eye adducted or abducted. Upgaze and downgaze were limited. Levator function was evaluated at 0 mm with a marginal reflex distance of -1 in OU. On thin-section brain stem magnetic resonance imaging, the left abducens nerve was absent, and the right and left oculomotor nerves were severely hypoplastic. The oculomotor nerve was smaller than the acoustic nerve was, and this was interpreted as hypoplasia according to a previous method (Kim and Hwang, Ophthalmology 2005;112:728-32). The medial and superior recti of OU were atrophic. CONCLUSIONS: A patient with congenital fibrosis of the extraocular muscles may show alternatively either synergistic divergence or adduction, which has not been documented before.
[Identification of a novel PHOX2A gene mutation in a Chinese family with congenital fibrosis of extraocular muscles type 2].
AbstractOBJECTIVE: To investigate potential mutation of PHOX2A (or ARIX) gene in a Chinese family affected with congenital fibrosis of extraocular muscles tyep 2 (CFEOM2). METHODS: Genomic DNA was obtained from affected and unaffected members of the family. With an ABI PRSIM Linkage Mapping Set-MD10 kit, selected markers flanking the PHOX2A locus were used for linkage analysis. Exons of PHOX2 gene were amplified and sequenced. A total of 100 normal subjects were recruited as controls. RESULTS: Genetic linkage was found at 11q13 between D11S4151 and D11S1320 and the PHOX2A gene. DNA sequencing has identified a heterozygous mutation in the exon 2 of the gene (227T to G, N76K). The same mutation was not found in the unaffected and 100 normal controls. CONCLUSION: A mutation of the PHOX2A gene 227T to G is responsible for the onset of congenital fibrosis of extraocular muscles type 2 in this Chinese family.
Infantile esotropia in a family with <i>TUBB3</i> mutation associated congenital fibrosis of extraocular muscles
AbstractBACKGROUND: The TUBB3 gene has been reported to be associated with type 3 congenital fibrosis of the extraocular muscles (CFEOM). The clinical features of CFEOM3 that are linked to TUBB3 mutations are diverse, ranging from mild ptosis and limitation of extraocular movement to severe ocular motility problems and central nervous system abnormalities. MATERIALS AND METHODS: This was a single retrospective case report. RESULT: This case report describes a patient with infantile esotropia, who had a heterozygous variant in TUBB3 c.904 G > A (p.A302T) known to cause CFEOM3 and her family members, who presented with manifestations associated with CFEOM3. CONCLUSION: Given the diverse clinical features of CFEOM3, the possibility of the occurrence of CFEOM3 should be considered when there is a congenital abnormality of extraocular muscle movement and a positive family history.
Hong Kong Journal of Ophthalmology · 2014 · 0 citations · open access
A child with unilateral restrictive ophthalmoplegia
AbstractWe report the case of a child with a rare condition of congenital restrictive ophthalmoplegia affecting the right eye. The condition comprised unilateral fibrosis, blepharoptosis and enophthalmos but without the intraorbital mass typical of congenital orbital fibrosis which was once considered a rare form of congenital fibrosis of extraocular muscles. The history, clinical features of the condition, and current understanding of congenital fibrosis of extraocular muscles were reviewed.
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.
