DeCure for Myopathy, congenital, with structured cores and z-line abnormalities
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for myopathy, congenital, with structured cores and z-line abnormalities — 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 moduleMyopathy, congenital, with structured cores and z-line abnormalities 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 myopathy, congenital, with structured cores and z-line abnormalities 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
actinin alpha 2 (ACTN2) — ACTN2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4D1E · 3.5 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Congenital myopathies are a group of early-onset muscle disorders defined by weakness, hypotonia, and specific structural abnormalities within the myofiber, with normal to slightly elevated creatine kinase. The 2017 review notes that greater than 25 unique genetic causes have been identified, with inheritance patterns that may be dominant, recessive, or X-linked, and that de novo dominant mutations also occur. A 2011 study of 40 patients found centronuclear myopathy was the commonest (40%), followed by congenital fiber type disproportion (37.5%), with less common forms including myotubular myopathy (5%), nemaline myopathy (5%), central core disease (5%), multicore disease (2.5%), and congenital myopathy with tubular aggregate (5%). The 2007 review reported that in the preceding year, genes were discovered for some congenital myopathies for the first time, including beta-tropomyosin in cap disease and skeletal muscle alpha-actin in Zebra body myopathy, and that further genes were identified for conditions where other genes were already known, such as cofilin in nemaline myopathy and selenoprotein N in congenital fibre type disproportion.
The 2007 review also described clarification of pathobiology, including the basis of epigenetic effects: silencing of the normal allele in recessive central core disease and persistence of cardiac (fetal) alpha-actin in nemaline myopathy patients with no skeletal actin. The 1994 review stated that application of immunohistochemistry and molecular genetics had expanded knowledge of well-established conditions such as central core myopathy and centronuclear/myotubular myopathy. The 2011 study found that immunolabeling to desmin corresponded to morphological changes within the myofibers, while vimentin was negative in all patients, and concluded there is no combined role of these proteins in the disease process. The 2017 review notes that cardiac involvement has been reported, and that congenital myopathies are generally considered nonprogressive disorders, though age at onset and clinical severity can range from severely affected at birth to a milder later-onset disease.
No drug treatment is mentioned in any of these abstracts. The 2007 review states that increased understanding of the genes and pathobiology should ultimately lead to effective treatments, but no such treatments are described. What is still missing are any clinical trials, any tested therapies, and any patient stratification beyond histopathological categories. The field remains at the stage of genetic discovery and pathobiological clarification, with no evidence of a drug being repurposed or developed for these conditions.
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 · 1994 · 52 citations
Congenital myopathies
AbstractSeveral dozen congenital myopathies are defined by clinical and morphological criteria. The application of the current generation of scientific techniques including immunohistochemistry and molecular genetics has resulted in the expansion of our knowledge and understanding of the well-established conditions including central core myopathy and centronuclear/myotubular myopathy and allowed greater understanding of the interrelationships of some of the less common or less well-established conditions. In the near future molecular genetics may allow the identification of the specific gene defect in many of these diseases. This article reviews the major congenital myopathies and presents some of the information gained by application of new technology to these conditions.
Current Opinion in Neurology · 2007 · 45 citations
Congenital myopathies
AbstractPURPOSE OF REVIEW: The aim of this review is to provide an up-to-date personal analysis of current congenital myopathy research. RECENT FINDINGS: In the past year novel congenital myopathies have been suggested, genes have been discovered for some of the congenital myopathies for the first time (beta-tropomyosin in cap disease and perhaps skeletal muscle alpha-actin in Zebra body myopathy), further genes have been identified for congenital myopathies where other genes had already been found (cofilin in nemaline myopathy, selenoprotein N in congenital fibre type disproportion) and recessive myosin storage myopathy was associated with homozygous mutation of slow-skeletal/beta-cardiac myosin which was already known to be mutated in dominant myosin storage myopathy. There has been further clarification of the pathobiology of the congenital myopathies, including determination of the basis of epigenetic effects: silencing of the normal allele in recessive central core disease and persistence of cardiac (fetal) alpha-actin in nemaline myopathy patients with no skeletal actin. SUMMARY: The increased understanding of the genes and pathobiology of the congenital myopathies that is developing should ultimately lead to effective treatments.
Congenital myopathies: Clinical and immunohistochemical study
AbstractCongenital myopathies (CMs), a group of relatively non-progressive disorders presents with weakness and hypotonia of varying severity, morphologically recognized by specific structural abnormalities within the myofiber. This report presents the clinical and Histopathological features of 40 patients with CMs. Centronuclear myopathy was the commonest (40%) followed by congenital fiber type disproportion (37.5%). Other less common CMs included: myotubular myopathy (5%), nemaline myopathy (5%), central core disease (5%), multicore disease (2.5%) and congenital myopathy with tubular aggregate (5%). Immunolabeling to desmin corresponded to morphological changes within the myofibers while vimentin was negative in all the patients. There is no combined role of these proteins in the disease process.
Neurology Genetics · 2017 · 1 citations · open access
Establishing prevalence in rare neuromuscular diseases
AbstractCongenital myopathies (CMs) are a heterogeneous group of early-onset muscle disorders with weakness, distinct histopathologic features, and normal to slightly elevated creatine kinase (CK).1 The age at onset and clinical severity can be variable, ranging from severely affected at birth to a milder later-onset disease.2 Cardiac involvement has been reported.3,4 CMs are generally considered nonprogressive disorders. Three main categories are recognized within the classical CMs based on their typical histopathology: nemaline myopathy (NM), core myopathy, and centronuclear myopathy (CNM). Inheritance in CMs may be dominant, recessive, or X-linked. Greater than 25 unique genetic causes of CM have been identified and different types of mutations within the same gene (e.g., deletions, duplications, missense, nonsense, splice-site, and frameshift mutations) have been identified, as well as de novo dominant mutations.5
Cambridge University Press eBooks · 2021 · 0 citations
Congenital Myopathies
AbstractCongenital myopathies are recognized by the clinical features of weakness and hypotonia, which may be obvious at birth or develop within the first weeks or months of life, thus sharing some characteristics with the congenital muscular dystrophies (discussed in Chapter 53). Classification has been based historically on skeletal muscle pathology, which in many cases remains useful in initial clinical workup, directing the choice of more conclusive genetic analyses. The main categories of congenital myopathies are nemaline myopathy, core myopathy, centronuclear myopathy (including X-linked myotubular myopathy), and congenital fiber-type disproportion myopathy (CFTD; see Table 54.1) [1,2]. A variety of additional phenotypes and genotypes are sometimes considered to be congenital myopathies (GeneTable)[3] but are omitted from the discussion here.
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.
