DeCure for Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 — 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 intellectual disability), type B3 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 intellectual disability), type b3 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
In a 2015 series of nine unrelated individuals with GMPPB-associated dystroglycanopathy, the mildest case had normal strength at 25 years, while three severely affected children presented in infancy with intellectual disability and epilepsy. All muscle biopsies showed dystrophic changes and abnormal immunostaining for glycosylated α-dystroglycan. The common variant c.79G>C (p.D27H) was associated with a mild limb-girdle muscular dystrophy phenotype, whereas c.860G>A (p.R287Q) was associated with a relatively severe congenital muscular dystrophy typically involving brain development. Sixty-six percent of GMPPB families to date carried one of these two variants.
A 2018 report described a child with a novel homozygous nonsense mutation in B3GALNT2, presenting with severe neurological disease from birth including hypotonia, muscle weakness, elevated creatine kinase, microphthalmia and blindness, extensive brain malformations including massive hydrocephalus and diffuse cobblestone-lissencephaly, and pontocerebellar hypoplasia. The child also had refractory epilepsy in the form of epileptic spasms, epileptic encephalopathy, West syndrome, and sensorineural hearing loss. The authors noted that these findings could expand the phenotype of B3GALNT2-related dystroglycanopathy, which had previously been reported in only a few cases with variable severity from mild congenital muscular dystrophy to severe muscle-eye-brain disease.
A 2025 cross-sectional study from North India enrolled 42 children under 18 years with congenital muscular dystrophy. The most common subtype was COL6-related dystrophy (32%), followed by LAMA2-related dystrophy (26%), LMNA-related dystrophy (19%), α-dystroglycanopathy (9%), and CHKB-related dystrophy (5%). Among 33 children assessed during follow-up, 45% (19 children) could ambulate independently. The median Motor Function Measure score was 60 (IQR 33-74), Brooke score was 2 (IQR 1-4), and Vigno score was 6 (IQR 3-9). The median Medical Research Council sum score was 40 (IQR 29-47) and Vineland Social Maturity Scale score was 83.5 (IQR 64-86). Motor outcome and quality of life were worst affected in children with α-dystroglycanopathy and LAMA2-related dystrophy. The authors concluded that motor impairment in congenital muscular dystrophy is profound, with the majority of children non-ambulant and those with α-dystroglycanopathy most severely affected.
What is still missing is any trial of a specific drug or intervention for these dystroglycanopathy subtypes. The available literature remains descriptive, with no controlled treatment data, no repurposing candidates tested, and no stratification by genotype that could guide a future trial. Funding for natural history studies and for any interventional trial, even of an already-approved drug, is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Mutation · 2015 · 47 citations
<i>GMPPB</i>-Associated Dystroglycanopathy: Emerging Common Variants with Phenotype Correlation
AbstractMutations in GDP-mannose pyrophosphorylase B (GMPPB), a catalyst for the formation of the sugar donor GDP-mannose, were recently identified as a cause of muscular dystrophy resulting from abnormal glycosylation of α-dystroglycan. In this series, we report nine unrelated individuals with GMPPB-associated dystroglycanopathy. The most mildly affected subject has normal strength at 25 years, whereas three severely affected children presented in infancy with intellectual disability and epilepsy. Muscle biopsies of all subjects are dystrophic with abnormal immunostaining for glycosylated α-dystroglycan. This cohort, together with previously published cases, allows preliminary genotype-phenotype correlations to be made for the emerging GMPPB common variants c.79G>C (p.D27H) and c.860G>A (p.R287Q). We observe that c.79G>C (p.D27H) is associated with a mild limb-girdle muscular dystrophy phenotype, whereas c.860G>A (p.R287Q) is associated with a relatively severe congenital muscular dystrophy typically involving brain development. Sixty-six percent of GMPPB families to date have one of these common variants.
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.
Clinical and Genetic Landscape of Children With Congenital Muscular Dystrophies From North India
AbstractCongenital muscular dystrophies are inherited disorders defined by early-onset muscle weakness, motor delay, and dystrophic muscle pathology. This study aimed to report the clinical and genetic landscape of children with congenital muscular dystrophies from North India. Cognitive and motor outcomes and quality of life were evaluated during follow-up. In a cross-sectional study, 42 children aged <18 years with clinical and genetic diagnosis of congenital muscular dystrophy were enrolled. The most common congenital muscular dystrophy subtype was COL6 -related dystrophy (RD) (32%), followed by LAMA2 -RD (26%), LMNA -RD (19%), α-dystroglycanopathy (α-DG; 9%), and CHKB -RD (5%). Motor and cognitive outcomes were was assessed in 33 (78%) children during follow-up, 45% (n = 19) were able to ambulate independently. Median value of the Motor Function Measure (MFM) score was 60 (interquartile range [IQR] 33-74), Brooke was 2 (IQR 1-4), and Vigno score was 6 (IQR 3-9). The median Medical Research Council sum score was 40 (IQR 29-47) and Vineland Social Maturity Scale (VSMS) score was 83.5 (IQR 64-86). The motor outcome and quality of life were worst affected in children with α-DG and LAMA2-RD . Hence, in a cohort of children with congenital muscular dystrophy from North India, COL6 -RD and LAMA2 -RD were the most common congenital muscular dystrophy subtypes. Motor impairment in children with congenital muscular dystrophy is profound, the majority being nonambulant and the children with α-DG most severely affected.
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.
