DeCure for Congenital fibrosis of extraocular muscles
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital fibrosis of extraocular muscles — screening already-approved drugs against its 12-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongenital fibrosis of extraocular muscles maps to a 12-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 congenital fibrosis of extraocular muscles 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
HRas proto-oncogene, GTPase (HRAS) — HRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ELT · 1.66 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
Congenital fibrosis of the extraocular muscles (CFEOM) is a rare, non-progressive disorder in which normal contractile muscle tissue is replaced by collagen and dense fibrous tissue, with occasional areas of degenerated skeletal muscle. One 1978 pedigree traced general fibrosis syndrome through five generations. A 2014 review states that most cases are bilateral and isolated, though some patients have systemic findings. The condition is divided into three phenotypic groups: CFEOM1, CFEOM2, and CFEOM3. Primary responsible genes are KIF21A for types 1 and 3, and PHOX2A/ARIX for type 2. In a 2012 Chinese family with CFEOM2, linkage was found at 11q13 and a heterozygous mutation in exon 2 of PHOX2A (227T to G, N76K) was identified; the same mutation was absent in unaffected family members and 100 normal controls.
A 2009 case report describes a 7-year-old girl with CFEOM who had corrected visual acuities of 20/50 in both eyes, 12 prism diopters of exotropia at distance and near in primary position, limited upgaze and downgaze, and levator function of 0 mm with a marginal reflex distance of -1 in both eyes. On thin-section brain stem MRI, the left abducens nerve was absent, and both oculomotor nerves were severely hypoplastic. The medial and superior recti of both eyes were atrophic. This patient showed either synergistic divergence or adduction depending on gaze direction, a pattern not previously documented. A 2014 review notes that studies suggest abnormal innervation of the extraocular muscles is the cause of muscle fibrosis, and that early treatment is important because of the risk of amblyopia.
Surgical management attempts to achieve functional readjustment of ocular and lid position and abnormal head posture. The 1978 paper reported that surgical results were considered satisfactory when compared with the original position of the eyes and the backward head tilt. A 2025 case report on CFEOM1 mentions presenting possible treatments and limitations. No controlled trial data, no quantitative response rates, and no survival figures exist for any drug therapy in CFEOM. What is still missing are prospective surgical outcome studies with standardised measurements, any pharmacological intervention tested in humans, and patient stratification by genotype (KIF21A versus PHOX2A) to see whether phenotype predicts surgical or other response.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractCongenital fibrosis of the extraocular muscles is characterized by the replacement of normal contractile muscle tissue by fibrous tissue or fibrous bands in varying degrees. The clinical entities which result from the fibrous replacement can be classified under the following headings: general fibrosis syndrome, congenital fibrosis of the inferior rectus muscle with blepharoptosis strabismus fixus, vertical retraction syndrome and congenital unilateral fibrosis, enophthalmos, and blepharoptosis. Genetic factors may or may not be apparent. One pedigree with general fibrosis syndrome was traced through five generations. Light and electron microscopy demonstrated replacement of normal muscles by collagen and dense fibrous tissue with occasional areas of degenerated skeletal muscle. The surgical management attempts to achieve some functional readjustment of the ocular and lid position as well as the abnormal head posture. The surgical results were considered satisfactory when compared with the original position of the eyes and the backward head tilt.
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.
Turkish Journal of Ophthalmology · 2014 · 0 citations · open access
Konjenital Ekstraoküler Kas Fibrozisi
AbstractCongenital fibrosis of the extraocular muscles (CFEOM) is a rare disorder characterized by hereditary non-progressive restrictive strabismus and blepharoptosis. Although most of the cases are bilateral and isolated, some patients may have systemic findings. CFEOM is divided into three groups as CFEOM 1, 2, and 3 according to the phenotype. Primary responsible genes are KIF21A for CFEOM type 1 and 3 and PHOX2A/ARIX gene for CFEOM type 2. Studies suggest that abnormal innervation of the extraocular muscles is the cause of muscle fibrosis. Early treatment is important because of the risk of amblyopia. Surgery is the primary treatment option for strabismus and blepharoptosis. (Turk J Ophthalmol 2014; 44: 312-5)
Oftalmología clínica y experimental. · 2025 · 0 citations · open access
Fibrosis congénita de los músculos extraoculares
AbstractCongenital fibrosis of the extraocular muscles (CFEOM) is a genetic disorder that belongs to the congenital disorders of cranial disinervation and is characterized by a non-progressive restrictive ophthalmoplegia. The objective was to present the case of a patient with a CFEOM type 1 diagnosis based on clinical history, physical examination and substantiated by magnetic resonance imaging findings, presenting possible treatments and limitations.
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.
