DeCure for Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 — 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 moduleMuscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 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 muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a9 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
dystroglycan 1 (DAG1) — DAG1 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 udpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7E9K · 2.05 Å · ligand URIDINE-5'-DIPHOSPHATE (UDP). Experimental structure, not a prediction.
What the evidence adds up to
Only 11 patients with LARGE mutations had been reported by 2014. Four additional patients were described that year, all with brain abnormalities that overshadowed an initially mild muscle phenotype. One patient with a homozygous Cys443 mutation showed polymicrogyria overlaid by a continuous agyric surface on postmortem examination. The p.Glu509Lys mutation in another patient was thought to confer a milder phenotype. Gross deletions and rearrangements are an important mutational mechanism for LARGE.
The broader group of dystroglycanopathies now includes 18 known genes, with severity ranging from Walker-Warburg syndrome to adult-onset limb-girdle muscular dystrophy. Two Finnish women with muscle-eye-brain disease caused by POMGNT1 mutations were followed for almost 40 years. Their clinical picture remained stable from adolescence: severe intellectual and motor disability, limited communication, visual impairment, epilepsy, joint contractures, repeated bowel obstructions, tooth abrasion from bruxism, irregular sleep, and previously unreported hypothermic periods with excessive sleepiness.
No curative treatment exists for any congenital muscular dystrophy. Symptomatic care by a multidisciplinary team is recommended to maintain quality of life. The 2001 review states this plainly, and no later abstract reports any therapeutic intervention.
What is still missing is any clinical trial of a drug for this specific subtype, any funded effort to repurpose an existing compound, and any systematic patient stratification that might distinguish the few LARGE-mutation patients from the larger dystroglycanopathy group. The natural history data remain sparse, and no biomarker for drug response has been proposed.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Neuropathology & Experimental Neurology · 2014 · 52 citations · open access
Clinical, Pathologic, and Mutational Spectrum of Dystroglycanopathy Caused by<i>LARGE</i>Mutations
AbstractDystroglycanopathies are a subtype of congenital muscular dystrophy of varying severity that can affect the brain and eyes, ranging from Walker-Warburg syndrome with severe brain malformation to milder congenital muscular dystrophy presentations with affected or normal cognition and later onset. Mutations in dystroglycanopathy genes affect a specific glycoepitope on α-dystroglycan; of the 14 genes implicated to date, LARGE encodes the glycosyltransferase that adds the final xylose and glucuronic acid, allowing α-dystroglycan to bind ligands, including laminin 211 and neurexin. Only 11 patients with LARGE mutations have been reported. We report the clinical, neuroimaging, and genetic features of 4 additional patients. We confirm that gross deletions and rearrangements are important mutational mechanisms for LARGE. The brain abnormalities overshadowed the initially mild muscle phenotype in all 4 patients. We present the first comprehensive postnatal neuropathology of the brain, spinal cord, and eyes of a patient with a homozygous LARGE mutation at Cys443. In this patient, polymicrogyria was the predominant cortical malformation; densely festooned polymicrogyria were overlaid by a continuous agyric surface. In view of the severity of these abnormalities, Cys443 may be a functionally important residue in the LARGE protein, whereas the mutation p.Glu509Lys of Patient 1 in this study may confer a milder phenotype. Overall, these results expand the clinical and genetic spectrum of dystroglycanopathy.
Intrafamilial variability in <i>GMPPB</i> -associated dystroglycanopathy: Broadening of the phenotype
AbstractDystroglycanopathies are characterized by deficient O-mannosyl glycosylation of α-dystroglycan (αDG) and represent an expanding genetically, biochemically, and clinically heterogeneous group of muscular dystrophies. Currently, there are 18 known genes leading to forms of α-dystroglycan–related dystrophy (αDG-RD), ranging in severity from a Walker-Warburg phenotype with severe brain malformations and hypotonia to milder childhood- or adult-onset limb-girdle muscular dystrophy (LGMD) phenotypes with or without intellectual disability.1,2
American Journal of Medical Genetics Part A · 2019 · 4 citations
Two middle‐aged women with the Finnish variant of muscle‐eye‐brain disease (MEB)
AbstractMuscle-eye-brain disease (MEB) is a recessively inherited rare disease. Sixteen different gene mutations are known, with the most common mutations in the POMGNT1 gene. The disease is now called congenital muscular dystrophy-dystroglycanopathy type A3 (MDDGA3). It manifests itself as muscular dystrophy with eye and brain anomalies and intellectual disability. Previous clinical reports describe young patients. We have been able to follow two patients for almost 40 years. Their clinical picture has remained quite stable since adolescence, appearing as severe intellectual and motor disability, extremely limited communication skills, visual impairment, epilepsy, joint contractures, repeated bowel obstructions, teeth abrasion due to bruxism, an irregular sleep pattern and as a previously unreported feature hypothermic periods manifesting as excessive sleepiness.
Handbook of clinical neurology · 2001 · 0 citations
Towards a Flexible information Retrieval Approach based on the Context
AbstractThe congenital muscular dystrophies are a heterogeneous group of disorders in which weakness and dystrophic pattern on muscle biopsy are present at birth or during the first months of life. This chapter reviews the most common forms of congenital muscular dystrophies, including laminin α-2 (merosin) deficiency, Ullrich congenital muscular dystrophy, fukutin-related proteinopathy, rigid spine syndrome, and glycosylation disorders of α-dystroglycan. The latter group is often associated with neuronal migration defects including lissencephaly, pachygyria, cerebellar and brainstem abnormalities, and variable ocular anomalies. Typical clinical findings and underlying genetic defects are discussed to assist in the differential diagnosis and diagnostic work-up of patients with congenital muscular dystrophies. There are still no curative treatment options for patients with congenital muscular dystrophies but regular follow-up and symptomatic care by a multidisciplinary team considering the peculiarities of each disorder are important to maintain or improve patients' quality of life.
Muscular magnet resonance imaging (M-MRI) in α-Dystroglykanopathies – clinical course of two juvenile patients with LGMD2I and LGMD2M
AbstractIntroduction: α-Dystroglycanopathies are a heterogenous group of neuromuscular disorders caused by a hypoglycosilation of the membrane protein α-dystroglycan. Mutations in the genes FKRP, FCMD, POMT1, POMT2, POMGnT1 and LARGE can cause a highly variable clinical phenotype but also disclose a remarkably disease overlap. The clinical phenotype can range from severe congenital onset with brain malformations (e.g. Fukuyama muscular dystrophy) to relatively milder forms (e.g. LGMD2).
Alpha-dystroglycanopathies: Clinical and genetic variability
AbstractAims: Alpha-dystroglycanopathies show a broad clinical spectrum from mild limb girdle to severe congenital muscular dystrophy with brain and eye abnormalities. Currently, mutations in nine genes are known which lead to defective glycosylation of α-dystroglycan: FKTN, LARGE, FKRP, POMT1, POMT2, POMGnT1, DPM3, DPM2, WWP1, ISPD or encodes α-dystroglycan, DAG1.
Genotype and Phenotype in 34 Families with Genetically Confirmed Walker-Warburg Syndrome or Muscle Eye Brain Disease
AbstractAims: Walker-Warburg syndrome (WWS) and muscle–eye–brain disease (MEB) comprises the most severe end of congenital muscular dystrophies with defective O-glycosylation of α-dystroglycan. Both are characterized by prenatal or neonatal onset, severe structural brain and eye abnormalities, and profoundly disturbed psychomotor development. the aim of this study is to describe the genotype and phenotype of patients with genetically confirmed WWS or MEB.
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.
