DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital myopathy 22B, severe fetal — 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 moduleCongenital myopathy 22B, severe fetal 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 congenital myopathy 22b, severe fetal 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
sodium voltage-gated channel alpha subunit 4 (SCN4A) — SCN4A 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 2~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6AGF · 3.2 Å · ligand [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate (6OU). Experimental structure, not a prediction.
What the evidence adds up to
The 2024 report describes two fetuses with a severe congenital myopathy phenotype including hydrops fetalis, large cystic hygromas, bilateral talipes, and fetal akinesia in the second trimester. Exome sequencing identified compound heterozygous likely pathogenic variants in RYR1 in one fetus, and two likely pathogenic variants in NEB in the other. No drug treatment was administered or discussed in that study. The 2017 Danish cohort of 107 patients aged five years and older with congenital myopathy found that core histology was less common than expected, but no drug intervention was tested. The 1994 review notes that congenital myopathies are defined by clinical and morphological criteria and that molecular genetics may eventually identify specific gene defects, but it does not report any drug therapy. The 2020 report on a biallelic LINE insertion in HACD1 describes the diagnostic shift from muscle biopsy to genomics but again contains no treatment data. The 1991 paper on fetal drug therapy discusses ethical and regulatory constraints for in utero interventions generally, but does not name any drug for congenital myopathy or report any clinical results.
No drug has been tested in any published trial for congenital myopathy 22B, severe fetal, or for the RYR1- or NEB-related fetal presentations described. The 2024 case series is limited to two fetuses, and the genetic diagnoses were used only for counselling, not for treatment. The 2017 prevalence study included no therapeutic intervention. The 1994 and 2020 reviews are purely descriptive. There is no evidence of any pharmacological agent having been administered to a fetus or infant with this condition in the peer-reviewed literature.
What is missing is any funded clinical trial, any drug repurposing screen, any animal model of the specific fetal phenotype, and any attempt to stratify patients by mutation type or severity. Without these, no drug can be evaluated for safety or efficacy in congenital myopathy 22B, severe fetal.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2008 · 72 citations
Congenital myopathies
AbstractPURPOSE OF REVIEW: The present review aims to discuss the pathological and clinical heterogeneity of congenital myopathies, and the overlap between the different variants highlighted by recent studies. RECENT FINDINGS: The spectrum of pathological changes associated with known gene defects has widened, and new genes responsible for rare structural defects have been identified. The complexity of the classification of these conditions is highlighted by the realization that defects in the same gene can result in diverse phenotypes, including disorders traditionally classified as congenital myopathies with structural abnormalities, adult-onset disorders, conditions characterized by distal weakness and wasting, or distal arthrogryposis. There is a wider appreciation of the complexities of inheritance and of the value of noninvasive assessment, such as muscle MRI. New animal models provide a better understanding of pathogenesis and are highlighting therapeutic possibilities. SUMMARY: The overlap of clinical and pathological features in the congenital myopathies has led to the recognition that diverse disorders are often associated with the same causative gene, and is challenging traditional classifications. Identification of further causative genes and development of new models will further the understanding of pathogenesis and development of therapies.
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.
Neurology Genetics · 2017 · 52 citations · open access
Phenotypes, genotypes, and prevalence of congenital myopathies older than 5 years in Denmark
AbstractOBJECTIVE: Congenital myopathy as a nosologic entity has long been recognized, but knowledge of overall and subtype prevalence and phenotype-genotype relationship is scarce, especially in the adult population. METHODS: A national cohort of 107 patients ≥5 years diagnosed with congenital myopathy were prospectively assessed clinically, histologically, and genetically. RESULTS: mutations. CONCLUSIONS: mutations and less core histology were present in our cohort. These differences may be explained by our prospective design, the older cohort of patients, and by differences in genetic background.
Characterization of congenital myopathies at a Korean neuromuscular center
AbstractINTRODUCTION: Congenital myopathies are muscle diseases characterized by specific histopathologic features, generalized hypotonia from birth, and perinatal complications, although some cases develop during childhood or, rarely, in adulthood. We undertook this study to characterize congenital myopathies among patients registered at our institution. METHODS: Clinical, histopathologic, and genetic features were evaluated in 34 patients recruited for this study. RESULTS: The majority of patients experienced a childhood onset, and no disease-related mortality was recorded during follow-up. Functional outcomes were no better for those with late-onset disease, indicating later disease progression can be significant. Nemaline myopathy was the most frequent pathology, followed by central core disease and centronuclear myopathy. Among the 18 (54.5%) genetically confirmed patients, NEB and RYR1 mutations were the most common, followed by DNM2 mutations. DISCUSSION: This study shows features not previously reported and suggests that congenital myopathy should be considered an important issue among adult patients. Muscle Nerve 58: 235-244, 2018.
Neurology Genetics · 2020 · 8 citations · open access
Biallelic LINE insertion mutation in <i>HACD1</i> causing congenital myopathy
AbstractCongenital myopathies are clinically and genetically heterogeneous, resulting from mutations in at least 30 different genes.1 The classical presentation is neonatal hypotonia and nonprogressive weakness with normal creatine phosphokinase, although there is a broad range in terms of age at onset and clinical presentation. Historically, congenital myopathies have been defined and diagnosed based on muscle biopsy. However, with advances in genomics, genetics have taken primacy in the diagnostic pathway.2
Prenatal Diagnosis · 2024 · 2 citations · open access
Lethal multiple pterygium syndrome, large cystic hygroma, and cleft palate: Rare and severe fetal presentations of <i>RYR1</i>‐ and <i>NEB‐</i>related congenital myopathies
AbstractCongenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present broadly. The most severe presentation is neonatal with arthrogryposis and, rarely, fetal akinesia and pterygia, features also seen in lethal multiple pterygium syndrome (LMPS). We describe two fetuses with similar phenotype, including hydrops fetalis, large cystic hygromas, bilateral talipes, and fetal akinesia in the second trimester. Genetic diagnoses were made using exome sequencing. Both fetuses had a severe form of congenital myopathy. In the first fetus, we identified two novel compound heterozygous likely pathogenic variants consistent with autosomal recessive RYR1-related congenital myopathy (congenital myopathy 1B). In the second fetus, we identified two likely pathogenic variants, one of which is novel, likely in trans consistent with a diagnosis of autosomal recessive NEB-related congenital myopathy. Reaching a genetic diagnosis for these fetuses allowed the families to receive accurate genetic counseling for future pregnancies. These fetuses highlight the genetic and phenotypic heterogeneity of LMPS, and support a broad approach to genetic testing.
Research Involving Fetal Drug Therapy: Ethical, Legal, and Practical Considerations
AbstractFetal drug therapies have emerged as a promising avenue for the prevention or correction of disease during fetal or immediate postnatal life. Despite slow progress, several medications have been developed for in utero therapy of disorders which relate to fetal and neonatal pulmonary, cardiac, neurologic, and growth disorders. However, ethical and regulatory constraints require protection of the mother and fetus while causing no more than necessary additional risk. Appreciating these constraints will lead to the identification of pragmatic questions which should be answered before evaluating the efficacy and safety of a particular treatment or research proposal.
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.
