DeCure for Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 — 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 moduleMuscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 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 muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type b1 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
Mutations in GMPPB, a catalyst for GDP-mannose production, cause muscular dystrophy through abnormal glycosylation of α-dystroglycan. In a 2015 series of nine unrelated individuals, the mildest case had normal strength at 25 years, while three severely affected children presented in infancy with intellectual disability and epilepsy. Muscle biopsies in all subjects were dystrophic with abnormal immunostaining for glycosylated α-dystroglycan. The common variant c.79G>C (p.D27H) was associated with a mild limb-girdle phenotype, whereas c.860G>A (p.R287Q) was associated with severe congenital muscular dystrophy typically involving brain development. Sixty-six percent of GMPPB families to date carried one of these two variants.
A 2025 study of B3GALNT2-related α-dystroglycanopathy analysed three newly diagnosed Chinese patients and 28 previously reported cases. All three new 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 showed 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-dystroglycan glycosylation and loss of laminin binding, consistent with a functional threshold effect. Transcriptomic analysis revealed upregulation of CHST10 in two patients.
A 2025 cross-sectional study of 42 children with congenital muscular dystrophy from North India found that α-dystroglycanopathy accounted for 9% of cases. Among 33 children assessed during follow-up, 45% could ambulate independently. The median Motor Function Measure score was 60 (IQR 33–74), Brooke score 2 (IQR 1–4), and Vigno score 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.
No drug-repurposing candidates have been tested in any clinical trial for this specific disease. A 2023 review of drug repositioning in muscular dystrophies notes that effective treatments have yet to be developed despite identification of genetic origins and knowledge of pathophysiological alterations, and that drug repositioning remains a theoretical approach based on previously available safety and pharmacokinetic data. What is missing is any funded clinical trial, any validated biomarker for patient stratification, and any preclinical evidence that a repurposed drug can restore α-dystroglycan glycosylation or laminin binding in human cells carrying GMPPB or B3GALNT2 mutations.
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.
Atypical facet of Möbius syndrome: Association with facioscapulohumeral muscular dystrophy
AbstractWe describe a patient with facioscapulohumeral muscular dystrophy (FSHD) associated with Möbius syndrome and congenital ophthalmoplegia. This 7-year-old girl had profound limitation of extraocular movements since birth, congenital facial diplegia, neonatal hypotonia, and progressive limb-girdle weakness. FSHD genetic testing revealed a pathogenic haplotype with a D4Z4 repeat of 30 kb. The father carries the same allele, although is minimally affected. This unusual case expands the genotypic-phenotypic spectrum of FSHD.
Journal of Inborn Errors of Metabolism and Screening · 2023 · 5 citations · open access
Dystroglycanopathies: Genetic Bases of Muscular Dystrophies Due to Alteration in the O-Glycosylation of α-Dystroglycan
AbstractCongenital muscular dystrophies (CMDs) are inherited, progressive and heterogeneous muscle disorders. A group of CMDs are dystroglycanopathies, also called α-dystroglycanopathies, where there is an abnormal glycosylation of protein α-dystroglycan. Hypoglycosylation of α-DG results in different severities of congenital muscular dystrophies and they present with progressive muscle weakness and loss of motor functions. This article first focuses on the CMDs, their classification according to the observed symptoms or the protein involved in the resulting phenotype. We then focus on dystroglycanopathies, the importance of its correct O-glycosylation of the α-dystroglycan given its important structural function, considering the enzymes involved in said glycosylation and the phenotypes that can result, to finally address current therapeutics for these diseases with the aim of increasing current knowledge.
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.
IntechOpen eBooks · 2023 · 0 citations · open access
The Potential Benefits of Drug-Repositioning in Muscular Dystrophies
AbstractMuscular dystrophies (MDs) are a complex group of rare neuromuscular disorders caused by genetic mutations that progressively weaken the muscles, resulting in an increasing level of disability. The underlying cause of these conditions consists of mutations in the genes in charge of a person’s muscle composition and functionality. MD has no cure, but medications and therapy can help control symptoms and slow the disease’s progression. Effective treatments have yet to be developed, despite the identification of the genetic origins and a thorough knowledge of the pathophysiological alterations that these illnesses induce. In this scenario, there is an urgent need for novel therapeutic options for these severe illnesses, and drug repositioning might be one feasible answer. In other words, drug repositioning/repurposing is an accelerated method of developing novel pharmaceuticals since the new indication is based on previously accessible safety, pharmacokinetic, and manufacturing data. This is particularly crucial for individuals with life-threatening illnesses such as MDs, who cannot wait for a conventional medication development cycle. This chapter aims to review the challenges and opportunities of drug-repositioning in a variety of MDs to establish novel treatment approaches for these incurable diseases.
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.
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.
