DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for progressive external ophthalmoplegia — 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 moduleProgressive external ophthalmoplegia 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 progressive external ophthalmoplegia 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
DNA polymerase gamma, catalytic subunit (POLG) — POLG 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 dcpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8D33 · 2.46 Å · ligand 2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE (DCP). Experimental structure, not a prediction.
What the evidence adds up to
A 2007 study of one large family identified three novel heterozygous POLG1 gene substitutions linked to autosomal dominant progressive external ophthalmoplegia and, in a single patient, parkinsonism. The coding mutations altered conserved amino acids in the linker region of polymerase gamma. None of the substitutions were found in 192 control chromosomes, 108 other PEO patients, or 140 sporadic Parkinson disease cases. The authors concluded that both conditions can be caused by mutations directly affecting the polymerase domain of polymerase gamma.
A 1975 analysis of 50 patients with chronic progressive external ophthalmoplegia found the group to be clinically, genetically, and histologically heterogeneous. The authors saw no justification for separating out distinctive subgroups, except possibly patients with "ophthalmoplegia plus" who also had central or peripheral nervous system abnormality. They concluded that CPEO represents a number of different degenerative disorders whose common denominator is ophthalmoplegia, with no adequate criteria for further classification at that time. A 1985 report described a family where CPEO was associated with dominant optic atrophy and progressive sensorineural deafness, which the authors considered an unusual manifestation of ophthalmoplegia plus.
A 1995 case report described one patient with CPEO given Coenzyme Q10 300 mg daily for three years, with a three-day trial of 200 mg daily after one year. Ocular ductions measured by synoptophore improved with treatment. The authors concluded Coenzyme Q10 was effective in limiting the severity of ophthalmoplegia in this single case. A 2020 review noted that PEO is a slowly progressive myopathy of extraocular muscles leading to frozen eyes without diplopia, with mitochondrial, autosomal dominant, or rarely autosomal recessive inheritance, and sporadic forms. Muscular involvement beyond extraocular muscles may occur years after onset, and there are scattered data on systemic signs.
What remains missing is a unified classification system for the heterogeneous presentations of PEO, large-scale prospective studies of non-ophthalmic manifestations, and any controlled trial of Coenzyme Q10 or other interventions. No drug has been tested in a randomised trial for this disease. Patient stratification by genotype and natural history is still absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 2007 · 83 citations
Mutation of the Linker Region of the Polymerase γ-1 (POLG1Gene Associated With Progressive External Ophthalmoplegia and Parkinsonism
AbstractOBJECTIVE: To define the molecular basis of the autosomal dominant progressive external ophthalmoplegia and parkinsonism in a large family with a dominantly transmitted multiple mitochondrial DNA deletion disorder. DESIGN: Microsatellite analysis and screening of the progressive external ophthalmoplegia 1 (PEO1), adenine nucleotide translocator 1 (ANT1), and polymerase gamma-1 (POLG1) genes. RESULTS: We identified 3 novel heterozygous POLG1 substitutions in the same family. Autosomal dominant progressive external ophthalmoplegia segregated with 1532G>A in exon 8 and an intronic variant c.2070 + 158G>A in cis. The one patient with parkinsonism had an additional heterozygous substitution in exon 7 in trans (1389G>T). Both coding region mutations were predicted to alter conserved amino acids in the linker region of polymerase gamma. None of the substitutions were found in 192 ethnically matched control chromosomes, 108 patients with progressive external ophthalmoplegia, nor 140 cases of sporadic idiopathic Parkinson disease. CONCLUSION: Both autosomal dominant progressive external ophthalmoplegia and parkinsonism can because caused by mutations that directly affect the polymerase domain of polymerase gamma.
AbstractThe clinical features and investigative findings of 50 patients with chronic progressive external ophthalmoplegia (CPEO) were analysed. The group was found to be clinically, genetically and histologically heterogeneous. With the possible exception of patients with "ophthalmoplegia plus," namely those who in addition to muscular weakness had evidence of central and/or peripheral nervous system abnormality, there was no apparent justification for separating out from among the group patients' subgroups which were distinctive enough to be recognized as syndromes. CPEO therefore seems to represent a number of different degenerative disorders whose common denominator is ophthalmoplegia and for which there are to date no adequate criteria for further classification.
Ophthalmic Paediatrics and Genetics · 1985 · 40 citations
Dominant optic nerve atrophy with progressive hearing loss and chronic progressive external ophthalmoplegia (CPEO)
AbstractThis paper describes a family where chronic progressive external ophthalmoplegia is associated with dominant optic atrophy and progressive sensorineural deafness. This may be a possible association in the same family of two diseases: progressive external ophthalmoplegia and dominant optic atrophy with progressive hearing loss. However, we believe that this family represents an unusual manifestation of ophthalmoplegia plus.
Australian and New Zealand Journal of Ophthalmology · 1995 · 7 citations · open access
Reversible ophthalmoplegia in CPEO
AbstractPURPOSE: To present a case of improvement of ocular motility in a patient with chronic progressive external ophthalmoplegia (CPEO) with Coenzyme Q10. METHODS: Coenzyme Q10 300 mg daily was given for three years with a three-day trial period of 200 mg daily after one year. Ocular ductions were measured by synoptophore. RESULTS: Ocular ductions improved with treatment with Coenzyme Q10. CONCLUSION: Coenzyme Q10, is effective in limiting the severity of ophthalmoplegia in this case.
Clinicogenetical Variants of Progressive External Ophthalmoplegia - An Especial Review of Non-ophthalmic Manifestations
AbstractProgressive external ophthalmoplegia (PEO) is a slowly progressive myopathy characterized by extraocular muscles involvement, leading to frozen eyes without diplopia. The pattern of inheritance may be mitochondrial, autosomal dominant or, rarely, autosomal recessive. Sporadic forms were also reported. Muscular involvement other than extraocular muscles may occur with varying degrees of weakness, but this mostly happens many years after the disease begins. There are also scattered data about systemic signs besides ophthalmoplegia. This article aims to review non-ophthalmic findings of PEO from a clinicogenetical point of view.
AbstractComplete bilateral external ophthalmoplegia is characterized by global weakness of the extraocular and levator muscles. It has a broad differential diagnosis, which varies depending on the tempo of onset. In this chapter, we review the approach to the patient with complete bilateral external ophthalmoplegia and discuss the common causes.
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.
