DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for oculopharyngodistal myopathy 2 — 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 2 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 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.
What the evidence adds up to
Oculopharyngodistal myopathy 2 (OPDM2) is one of four genetically defined subtypes of a rare hereditary muscle disease. The causative mutation is CGG repeat expansion in the 5'-untranslated region of the GIPC1 gene. The condition presents with slowly progressive ptosis, extraocular palsy, weakness of the masseter, facial and bulbar muscles, and distal limb weakness, typically starting around age 40 or later. Muscle biopsy shows rimmed vacuoles and intranuclear inclusions in myofibers, with small angular fibres also noted. One early autopsy found no remarkable changes in the central or peripheral nervous system.
No drug therapy has been tested or reported for OPDM2 specifically. The 2022 review states that management of OPDM is discussed but provides no specific treatment data. A 1979 case report described a 75-year-old French-Canadian woman with oculopharyngeal dystrophy whose first biopsy showed histopathology similar to idiopathic polymyositis, but a second biopsy 15 months later was consistent with the usual dystrophic pattern. This suggests a possible transient inflammatory phase in some patients, but no treatment was given or evaluated in that report.
The 2023 review of biological therapies for idiopathic inflammatory myopathies discusses intravenous immunoglobulin, rituximab, and Janus kinase inhibitors for refractory myositis with lung involvement or oropharyngeal dysphagia. That review concerns a different disease group — idiopathic inflammatory myopathies — not OPDM2. There is no evidence that these biologics have been studied in OPDM2 or any OPDM subtype.
What is missing is any clinical trial, any drug tested in OPDM2 patients, and any understanding of whether the transient inflammation seen in one patient is a general phenomenon. The exact pathogenic mechanism — whether RNA gain-of-function, protein gain-of-function, or repeat-mediated silencing — remains unclear, and no targeted therapy has been proposed. Funding for natural history studies and for trials that stratify patients by genotype and repeat length would be needed before any drug could be evaluated.
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.
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.
Rambam Maimonides Medical Journal · 2023 · 7 citations · open access
Biological Therapies in Inflammatory Myopathies
AbstractIdiopathic inflammatory myopathies (IIM) are a rare group of disorders that feature progressive immune-mediated skeletal muscle destruction along with skin, lung, and joint involvement. Management of IIMs necessitates glucocorticoid therapy followed by conventional steroid-sparing agents to control disease activity. In the settings of refractory myositis or life-threatening manifestations, e.g. lung involvement or oropharyngeal dysphagia, second-line therapies are needed to minimize disease burden, avoid end-organ damage and steroid toxicity, and decrease mortality. These therapies may include biological disease-modifying antirheumatic drugs (bDMARDs), and to a lesser extent, targeted synthetic disease-modifying antirheumatic drugs (TSD). This article reviews the current use of bDMARDs, e.g. intravenous immunoglobulin and rituximab, and a TSD-Janus kinase inhibitors (JAKI)-along with their indications, efficacy, and safety in managing IIM.
Neurology and Clinical Neuroscience · 2022 · 6 citations
Recent topics of oculopharyngodistal myopathy
AbstractAbstract Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease manifesting with progressive ocular, bulbar, and predominantly distal limb weakness. Muscle pathology is characterized by the presence of rimmed vacuoles and small angular fibers. To date, LRP12 , GIPC1 , NOTCH2NLC , and RILPL1 have been reported as the causative genes for OPDM, with the subtypes categorized according to each gene. The clinicopathological and genetic features (triplet repeats in 5′ untranslated region) are similar among all OPDM subtypes, suggesting a comparable pathogenesis among them. Several studies have demonstrated the possible pathomechanism of OPDM, such as protein/RNA gain‐of‐function theories. In this review, we summarized the recent advances in the molecular mechanism, clinicopathological findings, and management of the disease.
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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