DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for oculopharyngodistal myopathy 1 — 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 moduleOculopharyngodistal myopathy 1 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 oculopharyngodistal myopathy 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.
What the evidence adds up to
Oculopharyngodistal myopathy 1 is an autosomal dominant condition first described in 1977 as a slowly progressive myopathy starting around age 40 or later, with ptosis, extraocular palsy, weakness of masseter, facial and bulbar muscles, and distal limb involvement. No other neurological symptoms or organ disturbances were observed. One autopsy found no remarkable change in the central or peripheral nervous system, and muscle biopsies showed myopathic patterns without any specific change. A 1995 case report described a childhood-onset form that also developed chronic intestinal pseudo-obstruction, a gastrointestinal involvement not previously reported in this disease.
The pathological hallmark of oculopharyngodistal myopathy is rimmed vacuoles and intranuclear inclusions in myofibers. Four gene mutations have been identified as disease-causing: CGG repeats in the 5'-untranslated region of LRP12 (OPDM1), GIPC1 (OPDM2), NOTCH2NLC (OPDM3), and RILPL1 (OPDM4). Limited studies suggest that CGG repeat expansion within the pathogenic range may act through a gain-of-function mechanism at the RNA or protein level, while repeat expansion over a threshold may cause hypermethylation and transcriptional silencing, resulting in mild phenotype or asymptomatic carriers. More studies on the exact pathogenic mechanism are needed.
A 1979 case report of a 75-year-old French-Canadian woman with oculopharyngeal dystrophy (a related but distinct condition) showed histopathologic alterations similar to idiopathic polymyositis on one biopsy, but a second biopsy 15 months later was more consistent with previously reported cases. This suggests some patients may pass through an initial phase of secondary muscle inflammation. No treatment trials for oculopharyngodistal myopathy 1 were reported in any of these abstracts.
What is still missing: no clinical trials have been conducted for this disease, no drug has been tested in patients, and the exact pathogenic mechanism remains unknown. Patient stratification by specific gene mutation (OPDM1–4) has not been linked to any treatment response. Funding for natural history studies and preclinical work on the CGG repeat mechanism is lacking.
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 · 1977 · 119 citations
Oculopharyngodistal Myopathy
AbstractAn autosomal dominant, heredofamilial myopathy consisted of slowly progressive ptosis and extraocular palsy, and weakness of the masseter, facial, and bulbar muscles, as well as distal involvement of the limbs starting around 40 years of age or later. No other neurological symptoms or disturbances of other organs or tissues were observed. In one case, autopsy disclosed no remarkable change in the central and peripheral nervous system, and muscle biopsy specimens from all patients showed myopathic patterns without any specific change. A descriptive term, "oculopharyngodistal myopathy," was proposed to separate the present illness from other ocular myopathies.
Childhood‐onset oculopharyngodistal myopathy with chronic intestinal pseudo‐obstruction
AbstractOculopharyngodistal myopathy is characterized by the adult onset of ptosis, external ophthalmoplegia, dysphagia, and distal weakness. Although dysphagia is common, other gastrointestinal involvement has not been described. We report a case with childhood onset who developed chronic intestinal pseudo-obstruction. Other myopathies associated with ophthalmoplegia and intestinal pseudo-obstruction such as mitochondrial cytopathies were excluded. Whether oculopharyngodistal myopathy is a variant of oculopharyngeal muscular dystrophy or a distinct neuromuscular disorder is unknown and requires further study.
CONTINUUM Lifelong Learning in Neurology · 2019 · 26 citations
Toxic Myopathies
AbstractPURPOSE OF REVIEW: This article reviews the pathogenesis, clinical features, and management of toxic myopathy related to common medications, critical illness, and illicit substances. RECENT FINDINGS: Muscle symptoms are common among statin users and are usually reversible after discontinuation of the statin; rarely, however, statins trigger an immune-mediated necrotizing myopathy that persists and requires immunomodulatory therapy. Autoantibodies targeting 3-hydroxy-3-methylglutaryl coenzyme A reductase can distinguish the toxic and immune-mediated forms. Immune checkpoint inhibitors, increasingly used in the treatment of advanced cancer, have recently been associated with the development of inflammatory myositis. A reversible mitochondrial myopathy has long been associated with zidovudine, but recent reports elucidate the risk of myopathy with newer antivirals, such as telbivudine and raltegravir. SUMMARY: The medications most commonly associated with myopathy include statins, amiodarone, chloroquine, hydroxychloroquine, colchicine, certain antivirals, and corticosteroids, and myopathy can occur with chronic alcoholism. Certain clinical, electrodiagnostic, and histologic features can aid in early recognition. Stopping the use of the offending agent reverses symptoms in most cases, but specific and timely treatment may be required in cases related to agents that trigger immune-mediated muscle injury.
Inflammatory myopathy in oculopharyngeal dystrophy
AbstractA 75-year-old French-Canadian woman with familial oculopharyngeal dystrophy demonstrated histopathologic alterations similar to those of idiopathic polymyositis. A second biopsy obtained 15 months later was more consistent with previously reported cases. It is suggested that certain patients with oculopharyngeal dystrophy may pass through an initial phase of secondary muscle inflammation similar to that seen in some other heritable myopathies.
Journal of Pediatric Orthopaedics · 2007 · 22 citations
Orthopaedic Complications of Myotubular Myopathy
AbstractMedial displacement of the navicular has been considered a major explanation for residual forefoot adduction (FFA) in congenital clubfoot and also a frequent reason for dissatisfaction after limited surgery. In this study, it was hypothesized that there would be an association between the degree of medial displacement of the navicular and residual FFA in clubfeet. The position of the navicular was retrospectively measured by ultrasonography in 49 clubfeet in 35 children at ages 3 to 6 years and correlated to residual FFA measured on footprints and radiographs (talo-first metatarsal angle). In the 49 clubfeet, the navicular was significantly more medially displaced toward the medial malleolus than in the 21 contralateral normal feet (P < 0.001). However, there was no correlation between the degree of medial displacement of the navicular and the degree of FFA measured on footprints (P = 0.690) or on radiographs (P = 0.390). Thus, there were clubfeet with straight forefoot and a medially displaced navicular, that is, "spurious correction," and clubfeet with FFA and the navicular in correct position in relation to the head of the talus. Both patient satisfaction and foot score declined with larger FFA. The results support the view that ultrasonography is a helpful tool for assessing the position of the navicular. The critical issue for analysis is whether the FFA is due to malalignment in the talonavicular joint or more distally.
Current Opinion in Neurology · 2022 · 22 citations
Oculopharyngodistal myopathy
AbstractPURPOSE OF REVIEW: Oculopharyngodistal myopathy (OPDM) is a rare adolescent or adult-onset neuromuscular disease that is characterized by progressive ocular, facial, pharyngeal and distal limb muscle weakness. The rimmed vacuoles and intranuclear inclusions in myofibers constitute the pathological hallmark of OPDM. In this review, the latest findings related to the genetic, molecular and clinical features of OPDM, as well as the diagnosis and management are summarized. RECENT FINDINGS: Four gene mutations, CGG repeats in the 5'-untranslated region of LRP12 , GIPC1 , NOTCH2NLC and RILPL1 have been reported to be disease-causing genes in OPDM, namely OPDM1, OPDM2, OPDM3 and OPDM4, accordingly. So far, limited studies have suggested that CGG repeat expansion within the pathogenic range may play a key role in the pathogenesis of OPDM with the gain-of-function mechanism at the RNA and/or protein level, while repeat expansion over a threshold limit may cause hypermethylation, leading to the transcriptional silencing of the CGG repeats in the expanded allele, which results in the existence of mild phenotype or asymptomatic carriers. SUMMARY: Novel gene mutations, possible molecular mechanisms and the clinical features related to different causative genes are discussed in this review. More studies on the exact pathogenic mechanism are needed.
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.
