DeCure for Autosomal recessive limb-girdle muscular dystrophy type 2U
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive limb-girdle muscular dystrophy type 2U — 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 2U 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 2u 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
dystroglycan 1 (DAG1) — DAG1 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 7E9K · 2.05 Å · ligand URIDINE-5'-DIPHOSPHATE (UDP). Experimental structure, not a prediction.
What the evidence adds up to
The 1994 paper that first mapped a limb-girdle muscular dystrophy locus to chromosome 2p studied two large inbred families and reported a maximum lod score of 3.57 at zero recombination with markers D2S134 and D2S136. Onset was in the pelvic girdle in the late teens with usually slow progression. That locus later became known as LGMD2B, caused by mutations in the dysferlin gene. A 2018 case report from Saudi Arabia described a patient with a rare homozygous duplication c.164dupA in DYSF and confirmed that no curative treatment exists; the authors stressed that accurate diagnosis matters because steroids and immunosuppressive medications are not effective and can cause side effects. No drug therapy was tested or recommended in that report.
A 1998 study excluded linkage to all known dominant and recessive LGMD loci in four dominant pedigrees, underscoring the genetic heterogeneity that complicates any single treatment approach. A 2023 review counted 31 LGMD subtypes (5 dominant, 26 recessive) and noted that the field is rapidly expanding in diagnosis and targeted treatment options, but it did not report results of any completed drug trial for LGMD2U specifically. A 2020 review on muscular dystrophies stated that gene therapy research is concentrating on recessive disorders, with the idea of complementing defective genes with an extra copy, and that mutations in each sarcoglycan component cause autosomal recessive LGMD variants. No clinical trial data for LGMD2U were presented.
What is still missing is any completed or ongoing clinical trial that tests a specific drug or gene therapy in patients with genetically confirmed LGMD2U. The natural history of the subtype remains poorly characterised, no patient stratification criteria have been validated, and no funding for a dedicated trial has been reported.
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.
Progress towards gene therapy for Duchenne muscular dystrophy
AbstractAbstract Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by defects in the dystrophin gene. Patients exhibit progressive muscle degeneration, generally begin using a wheelchair before 11 years of age, and die from respiratory or cardiac failure by their early to mid-twenties. Currently no treatment is available for this disease that affects 1 in 3500 newborn males worldwide. As a result, intensive efforts are under way to develop methods to treat DMD by gene therapy. This Commentary will present some of the successes of this research and identify a few of the most challenging obstacles to be overcome before effective treatment is available. Success in treating any disorder by gene therapy hinges on a thorough understanding of the biological parameters of the disease process and the tissues involved. Much of this groundwork has been laid for DMD, and this research effort can serve as a paradigm for the assault
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.
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.
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.
