DeCure for Autosomal recessive limb-girdle muscular dystrophy type 2Y
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive limb-girdle muscular dystrophy type 2Y — 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 moduleAutosomal recessive limb-girdle muscular dystrophy type 2Y 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 autosomal recessive limb-girdle muscular dystrophy type 2y 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
torsin 1A interacting protein 1 (TOR1AIP1) — TOR1AIP1 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 4TVS · 1.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In 1994, linkage to markers D2S134 and D2S136 on chromosome 2p was identified in two large inbred families with autosomal recessive limb-girdle muscular dystrophy, with a maximum lod score of 3.57 at zero recombination. The phenotype in those families showed onset in the pelvic girdle musculature in the late teens and usually relatively slow progression. This work identified a second locus for autosomal recessive limb-girdle muscular dystrophy, later designated type 2Y.
A 2018 case report from Saudi Arabia described a patient with limb-girdle muscular dystrophy type 2B caused by a rare homozygous duplication c.164dupA, p.(Ile57Hisfs*8) in the dysferlin gene (DYSF). The authors stated there is no curative treatment for this disease and emphasised that accurate diagnosis is important to avoid using steroids and immunosuppressive medications, which are not effective and may have several side effects. No drug therapy was tested or reported in that study.
A 1998 study of four large autosomal dominant limb-girdle muscular dystrophy families excluded linkage to all known dominant loci and also found no evidence for linkage to any of the seven recessive LGMD loci known at that time. A 2020 review noted that research into gene therapy for muscular dystrophies is concentrating on recessive disorders, with the idea of complementing defective genes with an extra copy, but no such therapy has been reported for limb-girdle muscular dystrophy type 2Y specifically.
What is still missing: no clinical trials have been conducted for any drug in limb-girdle muscular dystrophy type 2Y; the natural history and patient stratification remain poorly defined; funding for preclinical work and for assembling sufficiently large, genetically confirmed patient cohorts is lacking.
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 Molecular Genetics · 1994 · 193 citations
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.
Journal of Back and Musculoskeletal Rehabilitation · 2018 · 9 citations
Limb-girdle muscular dystrophy type 2B: An unusual cause of proximal muscular weakness in Saudi Arabia
AbstractDysferlinopathies encompass a group of neuromuscular diseases characterized by the absence of dysferlin in skeletal muscle. It is a genetic disorder caused by a mutation in the dysferlin gene (DYSF) with an autosomal recessive mode of inheritance. In this article, we report a case of Limb-girdle muscular dystrophy type 2B with a rare homozygous duplication c.164dupA, p.(Ile57Hisfs*8) (rs863225020) in DYSF in a Saudi patient. To the best of our knowledge, this is the first case from Saudi Arabia with complete clinical data, pathology findings, radiology findings, and genetic analysis. Although there is no curative treatment for this disease, an accurate diagnosis is important to avoid using steroids and immunosuppressive medications, which are not effective and may have several side effects. Further studies are needed to explore potential therapies for this rare condition.
Exclusion of Identified LGMD1 Loci from Four Dominant Limb-Girdle Muscular Dystrophy Families
AbstractThe limb-girdle muscular dystrophies are a clinically and genetically heterogeneous group of disorders. Recent linkage analyses and positional cloning studies have identified numerous loci responsible for the recessive and dominant forms, underscoring the inherent heterogeneity. In this report, we investigate four large autosomal dominant limb-girdle pedigrees and exclude these pedigrees from linkage to these loci. In addition, there is no evidence for linkage to any of the seven recessive LGMD loci.
AbstractThe muscular dystrophies are genetically determined disorders characterized by progressive weakness and degeneration of muscle. Research into gene therapy in the muscular dystrophies is presently concentrating on the recessive disorders, with the idea that these might be treated by complementation of the defective genes with an extra copy. The gene responsible for X-linked Duchenne muscular dystrophy was the first defective gene to be isolated in the muscular dystrophies. A number of more direct strategies for genetic therapy of muscular dystrophies are currently being explored. Mutations in each component of the sarcoglycan complex, however, result in variants of autosomal recessive limb-girdle muscular dystrophy. Emery-Dreifuss muscular dystrophy is characterized by skeletal muscle weakness, joint contractures and a cardiomyopathy with arrhythmia. The recessive limb-girdle muscular dystrophy, LGMD2A, is caused by mutations in a gene on chromosome 15q15 that codes for the muscle-specific calcium-activated neutral protease, calpain-3.
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.
