DeCure for Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4 — 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 without intellectual disability), type B4 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 without intellectual disability), type b4 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.
What the evidence adds up to
In a 2015 report on intrafamilial variability in GMPPB-associated dystroglycanopathy, the authors note that the group of disorders known as dystroglycanopathies is defined by deficient O-mannosyl glycosylation of α-dystroglycan. At that time, 18 genes were known to cause forms of α-dystroglycan–related dystrophy, with severity ranging from a Walker-Warburg phenotype with severe brain malformations to milder childhood- or adult-onset limb-girdle muscular dystrophy with or without intellectual disability. No treatment or intervention is discussed.
A 2025 cross-sectional study from North India enrolled 42 children under 18 years with a clinical and genetic diagnosis of 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%). Motor and cognitive outcomes were assessed in 33 children during follow-up; 45% (19 children) could ambulate independently. The median Motor Function Measure score was 60 (interquartile range 33–74), Brooke score 2 (IQR 1–4), Vigno score 6 (IQR 3–9), Medical Research Council sum score 40 (IQR 29–47), and Vineland Social Maturity Scale score 83.5 (IQR 64–86). The authors state that motor outcome and quality of life were worst affected in children with α-dystroglycanopathy and LAMA2-related dystrophy, and that motor impairment was profound, with the majority being non-ambulant and those with α-dystroglycanopathy most severely affected.
A 2021 Chinese case report describes two patients with α-dystroglycanopathy caused by compound heterozygous mutations in POMT1 and POMT2. One patient had a c.824+1G>A splicing mutation and a c.1777G>A (p.A593T) mutation in POMT1; the other had c.604T>G (p.F202V) and c.868C>T (p.P290S) in POMT2. Both patients showed exercise retardation, with or without mental retardation, and serum creatine kinase was significantly increased. Electromyography showed myogenic impairment, and muscle biopsy was consistent with myopathy. One patient was diagnosed as congenital muscular dystrophy with mental retardation, the other as limb-girdle muscular dystrophy type 2N. The authors note that α-dystroglycanopathy is easy to misdiagnose and that genetic testing aids early diagnosis, prognosis, and genetic counselling. No treatment or outcome beyond diagnosis is reported.
Across these studies, no drug treatment or repurposing candidate is tested or proposed for any form of α-dystroglycanopathy. What is missing is any clinical trial of a pharmacological intervention, any funding for such a trial, and any stratification of patients by genotype or severity that might allow a targeted approach. The natural history data remain limited to small, geographically restricted cohorts, and no biomarker or surrogate endpoint has been validated for use in a trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2015 · 19 citations · open access
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
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.
POMT1 and POMT2 gene mutations result in 2 cases of <b>alpha-</b>dystroglycanopathy.
AbstractAlpha-dystroglycanopathy (α-DGP) is a group of congenital muscular dystrophy and limb band muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (α-DG). At present, there are few studies on the clinical manifestations, genetic characteristics, and diagnostic methods for α-DGP in China. Two cases of α-DGP caused by POMT1 and POMT2 gene mutations in the protein O-mannosyltransferases (PMTs) family were admitted to the Department of Pediatrics, Xiangya Hospital, Central South University. The 2 patients showed exercise retardation, with or without mental retardation. Serum level of creatine kinase (CK) was increased significantly. Electromyography showed myogenic impairment. Muscle biopsy was consistent with myopathy. Genetic test showed that both patients had compound heterozygous mutations, and the parents of the 2 patients were heterozygous with one of the mutations. There were c.824+1G>A, splicing and c.1777G>A, p.A593T in POMT1 gene, and c.604T>G, p.F202V and c.868C>T, p.P290S in POMT2 gene. The online database was used to predict the mutation sites and suggested the pathogenicity. Finally, one patient was diagnosed as congenital muscular dystrophy with mental retardation (CMD-MR) and the other was dystrophytype 2N (LGMD2N). PMTs family has similar sequences. Gene mutations can lead to different degrees of muscular dystrophy with the increase of serum level of CK. α-DG is easy to be misdiagnosed. Genetic examination is beneficial to early diagnosis, prognosis, and genetic counseling.
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.
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