DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for central core myopathy — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCentral core myopathy maps to a 2-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 central core myopathy 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
cytochrome b5 reductase 3 (CYB5R3) — CYB5R3 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 faddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1UMK · 1.75 Å · ligand FLAVIN-ADENINE DINUCLEOTIDE (FAD). Experimental structure, not a prediction.
What the evidence adds up to
Central core disease is an autosomal-dominant congenital myopathy linked to mutations in the RYR1 gene, but a 2007 study of nine Brazilian families found two carrying recessive RYR1 mutations; the heterozygous parents were asymptomatic and the affected patients were only mildly affected, suggesting recessive inheritance may be more common than previously appreciated. A 1979 family study described four members with congenital nonprogressive myopathy, two with adult-onset muscle weakness, and two with raised CPK levels but no weakness; one late-onset case worsened over eighteen months, with biopsy showing loss of type 2 fibres and appearance of type 3 fibres. A 1991 natural history study of five patients with minicore-multicore myopathy followed for 6 to 16 years found that four had improved muscle strength and one had deteriorated, with no distinguishing features to predict outcome.
Muscle imaging in 11 patients with RYR1-linked central core disease showed a characteristic pattern involving gluteus maximus, adductor magnus, sartorius, vastus intermediolateralis, soleus, and lateral gastrocnemius, while five patients from two families with core myopathies not linked to RYR1, ACTA1, or MYH7 had different patterns—one family showing gluteus minimus and hamstring involvement, the other affecting gluteus minimus, vastus intermediolateralis, tibialis anterior, and medial gastrocnemius. This indicates genetic heterogeneity and additional unidentified genes in autosomal dominant core myopathies. A 2019 review of toxic myopathies lists statins, amiodarone, chloroquine, hydroxychloroquine, colchicine, certain antivirals, and corticosteroids as common causes, with symptoms usually reversible after stopping the drug, except for statin-triggered immune-mediated necrotising myopathy which requires immunomodulatory therapy.
A 2019 study of 44 Korean patients with GNE myopathy—a separate disorder with rimmed vacuoles—found that wrist and neck were the last joints to lose antigravity function, two-thirds could walk independently or with aid, and patients with biallelic kinase domain mutations progressed more rapidly than those with epimerase and kinase domain mutations. No drug treatment for central core disease or related core myopathies is described in these abstracts. What remains missing are prospective natural history studies with standardised outcome measures, identification of the additional genes responsible for RYR1-unlinked core myopathies, and any clinical trials testing interventions—whether drug, gene therapy, or otherwise—in these patient populations.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Muscle & Nerve · 2007 · 52 citations
Central core disease due to recessive mutations in <i>RYR1</i> gene: Is it more common than described?
AbstractCentral core disease (CCD) is an autosomal-dominant congenital myopathy, with muscle weakness and malignant hyperthermia (MH) susceptibility. We identified two of nine Brazilian CCD families carrying two mutations in the RYR1 gene. The heterozygous parents were clinically asymptomatic, and patients were mildly affected, differing from the few autosomal-recessive cases described previously. Recessive inheritance in CCD may therefore be more common than previously appreciated, which has important implications for genetic counseling and MH prevention in affected families.
AbstractA family is described whose members showed different clinical presentations of central core disease. In 4 members the myopathy was congenital and nonprogressive, but in 2, muscle weakness first developed in adult life. Two further members had raised CPK levels without muscle weakness. Muscle weakness in one of the late-onset cases increased over eighteen months. This was associated with evidence of loss of type 2 fibres and the appearance of type 3 fibres on muscle biopsy. It is suggested that central core disease involves reinnervation of type 2 fibres by type 1 axons, and that the clinical manifestation of the disease depends on the age of onset and rate of progression of this process.
Muscle imaging in dominant core myopathies linked or unlinked to the ryanodine receptor 1 gene
AbstractOBJECTIVE: To characterize the muscle involvement of patients with central core disease (CCD) caused by mutations in the ryanodine receptor 1 gene (RYR1) and to compare these findings with those from patients with core myopathies unlinked to the RYR1 gene. METHODS: We performed a systematic muscular imaging assessment in 11 patients with an RYR1 gene mutation and compared these findings with those of 5 patients from two unrelated families with autosomal dominant core myopathies not linked to RYR1, ACTA1, or MYH7 gene loci. RESULTS: All patients with RYR1 CCD had a characteristic pattern with predominant involvement of the gluteus maximus, adductor magnus, sartorius, vastus intermediolateralis, soleus, and lateral gastrocnemius muscles. In contrast, muscle CT in the first family not linked to RYR1 showed predominant affection of the gluteus minimus and hamstring muscles, whereas the second family presented with predominant involvement of the gluteus minimus, vastus intermediolateralis, tibialis anterior, and medial gastrocnemius muscles. In addition to muscle imaging data, we present detailed information on the clinical and pathologic findings of these novel phenotypes of core myopathies not linked to RYR1. CONCLUSIONS: Our data suggest genetic heterogeneity in autosomal dominant core myopathies and the existence of additional unidentified genes.
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.
The natural history of minicore‐multicore myopathy
AbstractTo determine the natural history of minicore-multicore myopathy (MMM) we studied 5 patients who were found to have this disorder from 6 to 16 years ago. Four of these patients had improved muscle strength since their original assessment and one patient had deteriorated. There were no clinical electrophysiological or pathological features that distinguished this last patient from the others. We conclude, therefore, that most patients with MMM may be expected to improve as time passes but, for unknown reasons, a minority may deteriorate. This information should be helpful to clinicians in their prognostic advice to new patients.
Journal of Clinical Neurology · 2019 · 20 citations · open access
Progression of GNE Myopathy Based on the Patient-Reported Outcome
AbstractBACKGROUND AND PURPOSE: gene, and frequently accompanied by rimmed vacuoles in muscle pathology. The initial symptom of foot drop or hip-girdle weakness eventually spreads to all limbs over a period of decades. Recent advances in pathophysiologic research have facilitated therapeutic trials aimed at resolving the core biochemical defect. However, there remains unsettled heterogeneity in its natural course, which confounds the analysis of therapeutic outcomes. We performed the first large-scale study of Korean patients with GNE myopathy. METHODS: We gathered the genetic and clinical profiles of 44 Korean patients with genetically confirmed GNE myopathy. The clinical progression was estimated retrospectively based on a patient-reported questionnaire on the status of the functional joint sets and daily activities. RESULTS: The wrist and neck were the last joints to lose antigravity functionality irrespective of whether the weakness started from the ankle or hip. Two-thirds of the patients could walk either independently or with an aid. The order of losing daily activities could be sorted from standing to eating. Patients with limb-girdle phenotype showed an earlier age at onset than those with foot-drop onset. Patients with biallelic kinase domain mutations tended to progress more rapidly than those with epimerase and kinase domain mutations. CONCLUSIONS: The reported data can guide the clinical management of GNE myopathy, as well as provide perspective to help the development of clinical trials.
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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