DeCure for Autosomal recessive limb-girdle muscular dystrophy type 2B
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive limb-girdle muscular dystrophy type 2B — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAutosomal recessive limb-girdle muscular dystrophy type 2B maps to a 3-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 autosomal recessive limb-girdle muscular dystrophy type 2b 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
calpain 3 (CAPN3) — CAPN3 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6BDT · 2.3 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 2007 study of 40 French patients with confirmed dysferlin protein deficiency and DYSF gene mutations, only half presented with the two classic dysferlinopathy phenotypes: Miyoshi myopathy and limb-girdle muscular dystrophy type 2B (LGMD2B). The other half showed unusual presentations: 14 patients (35%) had a mixed proximodistal onset, 4 (10%) had a pseudometabolic myopathy, and 2 (5%) had only asymptomatic hyperCKemia. The disease could worsen rapidly, and 10 patients (25%) were initially misdiagnosed with polymyositis. The authors suggested a link between the proximodistal phenotype, inflammation, and severity, concluding that dysferlinopathies range from asymptomatic to severely disabling.
The LGMD2B locus was mapped to chromosome 2p in 1994, using two large inbred families of different ethnic origins. Linkage to markers D2S134 and D2S136 gave a maximum lod score of 3.57 at zero recombination. The phenotype in those families was similar: onset in the pelvic girdle musculature in the late teens, with usually relatively slow progression. This work identified a second locus for autosomal recessive limb-girdle muscular dystrophy, after LGMD2 on chromosome 15q.
A 2023 update on limb-girdle muscular dystrophies describes 31 subtypes in total: five autosomal dominant and 26 autosomal recessive. The review notes that the field is rapidly expanding in diagnosis and in targeted treatment options, but it does not report any specific drug trial results for LGMD2B. No therapy is mentioned that has shown efficacy in dysferlinopathy patients.
What is still missing for LGMD2B is a completed, adequately powered randomised controlled trial of any pharmacological agent. The clinical heterogeneity — ranging from asymptomatic hyperCKemia to rapid progression with misdiagnosis as polymyositis — means that patient stratification by phenotype, age at onset, and inflammatory status will be essential for any future trial. Funding for such a trial remains the primary barrier.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 2007 · 265 citations
Phenotypic Study in 40 Patients With Dysferlin Gene Mutations
AbstractOBJECTIVE: To describe the phenotypic spectrum of dysferlin (DYSF) gene mutations (which cause dysferlinopathies, autosomal recessive muscular dystrophies) in patients with a dysferlin protein deficiency. DESIGN: Clinical, biological, and pathological data from 40 patients were reviewed. The diagnosis of dysferlinopathy was based on the absence or strong reduction of dysferlin in muscle, and confirmed by mutational screening of the DYSF gene. SETTING: Two French neuromuscular diseases centers (in Paris and Marseilles). RESULTS: Two main dysferlinopathy phenotypes are well recognized: Miyoshi myopathy and limb-girdle muscular dystrophy type 2B. Typical Miyoshi myopathy and limb-girdle muscular dystrophy type 2B were found in 20 (50%) patients only. Unusual phenotypes included a mixed phenotype, referred to as "proximodistal," combining distal and proximal onset in 14 (35%) patients, pseudometabolic myopathy in 4 (10%), and asymptomatic hyperCKemia (an increased serum creatine kinase level) in 2 (5%). The disease may worsen rapidly, and 10 (25%) patients were initially misdiagnosed as having polymyositis. We suggest a relationship between proximodistal phenotype, inflammation, and severity. CONCLUSION: In addition to typical Miyoshi myopathy and limb-girdle muscular dystrophy type 2B, dysferlinopathies are a clinically heterogeneous group of disorders ranging from asymptomatism to severe functional disability.
A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p
AbstractThe limb-girdle muscular dystrophies are a clinically and genetically heterogeneous group of disorders. We have studied two large inbred families of different ethnic origin and excluded linkage to LGMD2 on chromosome 15q and SCARMD on chromosome 13. Proceeding to a genomic linkage search, we have now identified linkage to markers D2S134 and D2S136 on chromosome 2p (maximum lod score 3.57 at zero recombination). The phenotype in the two families was similar, with onset in the pelvic girdle musculature in the late teens and usually relatively slow progression. This work identifies a second locus for autosomal recessive limb-girdle muscular dystrophy.
Sri Lanka Journal of Neurology · 2023 · 0 citations · open access
Limb-girdle muscular dystrophies: An update
AbstractLimb-girdle muscular dystrophies (LGMDs) are a heterogenous group of genetically driven muscle disorders, which share the two common features of progressive, predominantly proximal girdle skeletal muscle involvement and dystrophic changes on pathology. This is a rapidly expanding landscape in neurology both in relation to diagnosis as well as evolving targeted treatment options. Thirty-one LGMD subtypes are described to date; five of autosomal dominant inheritance and 26 of autosomal recessive transmission. This article describes their pathogenesis, clinical presentation, diagnosis and recent therapeutic advances.
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.
