DeCure for Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 — 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 A3 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 a3 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
protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-) (POMGNT1) — POMGNT1 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 5GGI · 2.6 Å · ligand URIDINE-5'-DIPHOSPHATE (UDP). Experimental structure, not a prediction.
What the evidence adds up to
Mutations in B3GALNT2, POMGNT1, and POMT1 cause congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A3 (MDDGA3). One child with a novel homozygous nonsense mutation in B3GALNT2 presented with severe neurological disease from birth: hypotonia, muscle weakness, wasting, elevated creatine kinase, microphthalmia, blindness, massive hydrocephalus, diffuse cobblestone-lissencephaly, pontocerebellar hypoplasia, refractory epileptic spasms, epileptic encephalopathy, West syndrome, and sensorineural hearing loss. Two women with the Finnish variant of muscle-eye-brain disease (most common mutations in POMGNT1) were followed for almost 40 years; their clinical picture remained quite stable since adolescence, with severe intellectual and motor disability, extremely limited communication, visual impairment, epilepsy, joint contractures, repeated bowel obstructions, teeth abrasion from bruxism, irregular sleep, and previously unreported hypothermic periods manifesting as excessive sleepiness. A consanguineous family with two sisters with MDDGA1 (POMT1 mutations) showed variable clinical severity. A 2023 case report describes a patient with a POMGNT1 mutation and pathogenic variant criteria PVS1, PM2, PP5, presenting global developmental delay, midbrain atrophy, cerebral and cerebellar atrophy, cerebellar vermal and pontocerebellar hypoplasia, central hypotonia, distal muscle weakness, myopia, glaucoma, hydrocephalus, and distinctive facial features.
No treatment or intervention is tested or reported in any of these abstracts. All describe natural history, genotype-phenotype correlations, or diagnostic findings. The 2002 papers cited are not about MDDGA3 specifically but about dystroglycan-ligand interactions and brain dystroglycan deletion in mice, and they provide no clinical data on patients.
What is missing: any clinical trial, any drug tested in these patients, any preclinical therapy study, any biomarker validation for severity or progression, any systematic natural history study with standardised outcome measures, and any funding for such work. Patient numbers are tiny — single cases or two-patient series — and no stratification by specific mutation or residual enzyme activity has been used to predict course or eligibility for future therapies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neuropediatrics · 2018 · 26 citations
B3GALNT2-Related Dystroglycanopathy: Expansion of the Phenotype with Novel Mutation Associated with Muscle-Eye-Brain Disease, Walker–Warburg Syndrome, Epileptic Encephalopathy-West Syndrome, and Sensorineural Hearing Loss
AbstractAbstract Mutations in B3GALNT2, encoding a glycosyltransferase enzyme involved in α-dystroglycan glycosylation, have been recently associated with dystroglycanopathy, a well-recognized subtype of congenital muscular dystrophy (CMD). Only a few cases have been reported with B3GALNT2-related dystroglycanopathy with variable severity ranging from mild CMD to severe muscle-eye-brain disease. Here, we describe a child with a novel homozygous nonsense mutation in B3GALNT2. The affected child has severe neurological disease since birth, including muscle disease manifested as hypotonia, muscle weakness, and wasting with elevated creatine kinase, eye disease including microphthalmia and blindness, brain disease with extensive brain malformations including massive hydrocephalus, diffuse cobblestone-lissencephaly, deformed craniocervical junction, and pontocerebellar hypoplasia. The clinical and radiologic findings are compatible with a diagnosis of severe muscle-eye-brain disease and more specifically Walker–Warburg syndrome. A more distinct aspect of the clinical phenotype in this child is the presence of refractory epilepsy in the form of epileptic spasms, epileptic encephalopathy, and West syndrome, as well as sensorineural hearing loss. These findings could expand the phenotype of B3GALNT2-related dystroglycanopathy. In this report, we also provide a detailed review of previously reported cases with B3GALNT2-related dystroglycanopathy and compare them to our reported child. In addition, we study the genotype–phenotype correlation in these cases.
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.
Congenital Muscular Dystrophy-Dystroglycanopathy (MDDGA1) in a Consanguineous Family with Compound Heterozygous Mutations of the POMT1 Gene and Variable Clinical Severity
AbstractBackground/Purpose: Congenital muscular dystrophies-dystroglycanopathies with brain and eye anomalies (MDDGA) are genetically heterogeneous autosomal recessive disorders with characteristic brain and eye malformations and congenital muscular dystrophy. We report on a consanguineous family with two sisters with MDDGA1 in which homozygosity mapping failed to elucidate the causal mutation.
International Journal of Science and Research (IJSR) · 2023 · 0 citations · open access
Case Study on Rare Disease: Muscle Brain Eye Disease (Congenital Muscular Dystrophy-Dystroglycanopathy with Brain and Eye Anomalies, Type A3)
AbstractA case of Congenital muscular dystrophy-dystroglycanopathy which is Likely Compound Heterozygous in Nature. Including 3 types of Congenital muscular Dystroglycanopathy. Includes Type A3 With Muscle, Brain and Eye, Type B3 with intellectual Disability, Type C3 with Limb Girdle type of Muscular disability. This Patient Having prominent Clinical Features of Type A3 (Muscle brain Eye Disease). This Disorder associated with POMGNT1 mutation with some Pathogenic mutant variant (PVS1, PM2, PP5) lead to A rare autosomal recessive disorder with clinical outline of global developmental delay, midbrain atrophy, cerebral and cerebellar atrophy, cerebellar vermal and pontocerebellar hypoplasia, central hypotonia, distal muscle weakness in upper and lower limbs, and abnormal USG. So, basically this disorder characterized by muscle weakness (hypotonia), severe nearsightedness (myopia), glaucoma and brain abnormalities. They also have developmental delay and intellectual disability, a buildup of fluid in the brain (hydrocephalus), and distinctive facial feature. Multiple Neurological abnormalities.
Science of Aging Knowledge Environment · 2002 · 0 citations
Other Noteworthy Papers This Week
AbstractD. E. Michele, R. Barresi, M. Kanagawa, F. Saito, R. D. Cohn, J. S. Satz, J. Dollar, I. Nishino, R. I. Kelley, H. Somer, V. Straub, K. D. Mathews, S. A. Moore, K. P. Campbell, Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies. Nature 418 , 417-422 (2002). [Abstract] [Full Text] S. A. Moore, F. Saito, J. Chen, D. E. Michele, M. D. Henry, A. Messing, R. D. Cohn, S. E. Ross-Barta, S. Westra, R. A. Williamson, T. Hoshi, K. P. Campbell, Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature 418 , 422-425 (2002). [Abstract] [Full Text]
Journal of Neuromuscular Diseases · 2025 · 0 citations · open access
Pathogenic mechanisms and clinical insights into <i>B3GALNT2</i> -related alpha-dystroglycanopathies
AbstractBackground B3GALNT2 mutations cause α-dystroglycanopathy (α-DGP), a rare condition characterized by muscular dystrophy, brain malformations, and developmental delay. However, its pathogenic mechanisms remain poorly understood. To date, limited cases have been reported, and the pathogenic mechanisms remain incompletely understood. Methods Clinical and genetic data from 3 newly diagnosed Chinese patients and 28 patients previously diagnosed with B3GALNT2 -related α-DGP were analyzed. Using patient-derived fibroblasts, α-dystroglycan (α-DG) glycosylation and laminin-binding capacity were assessed by immunoblotting, laminin overlay and immunofluorescence. B3GALNT2 mRNA and protein levels were quantified by real-time PCR and immunoblotting. Enzymatic activity was measured using purified recombinant B3GALNT2 proteins. Differentially expressed genes were identified via an mRNA microarray. Results All three patients carried compound heterozygous variants involving one truncating and one missense mutation. Two novel mutations (c.657_658insTT and c.1384T > C) were identified. Functional studies confirmed that the missense mutations (Y436C and C462R) impaired enzymatic activity to 40–50% of wild-type levels, while splice variants caused frameshifts and likely complete loss of protein. Despite partial residual activity, all patients showed severely reduced α-DG glycosylation and loss of laminin binding, consistent with a functional threshold effect. Transcriptomic analysis revealed upregulation of CHST10 in two patients. Conclusions This study expands the mutational spectrum of B3GALNT2 -related α-DGP and provides mechanistic insight into the pathogenicity of novel variants. Our findings support a functional threshold model for B3GALNT2 activity in α-DG glycosylation and suggest CHST10 as a potential transcriptional responder to glycosylation defects. These results deepen the understanding of B3GALNT2 -related dystroglycanopathies and may inform future diagnostic and therapeutic strategies.
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.
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.
