DeCure for Autosomal recessive limb-girdle muscular dystrophy
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive limb-girdle muscular dystrophy — screening already-approved drugs against its 24-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 maps to a 24-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 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
protein O-glucosyltransferase 1 (POGLUT1) — POGLUT1 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 5L0V · 1.305 Å · ligand URIDINE-5'-DIPHOSPHATE (UDP). Experimental structure, not a prediction.
What the evidence adds up to
The 1998 study of four large families with autosomal dominant limb-girdle muscular dystrophy found no linkage to any of the known dominant loci, and also no evidence of linkage to any of the seven recessive LGMD loci then identified. This result underscores the genetic heterogeneity that has long been recognised in the limb-girdle muscular dystrophies, and it means that for those families the molecular cause remained unknown at that time. The 2012 and 2020 reviews confirm that the recessive forms, including those caused by sarcoglycan complex mutations and by calpain-3 mutations (LGMD2A), have been the main targets for gene therapy research, on the rationale that adding a working copy of the defective gene might compensate for the loss. No clinical trial results for any drug in autosomal recessive limb-girdle muscular dystrophy are reported in these abstracts.
The 2012 review states that new therapeutic approaches have led to clinical trials in the dystrophinopathies and limb-girdle dystrophies, but it gives no drug names, no patient numbers, no survival or response rates, and no outcomes. The 2020 review notes that gene therapy research is concentrating on recessive disorders, but again provides no trial data, no efficacy figures, and no mention of any specific compound that has been tested in patients. There is no evidence in these abstracts that any drug has shown benefit in autosomal recessive limb-girdle muscular dystrophy.
What is still missing is any completed, published clinical trial that reports a meaningful outcome — survival, muscle strength, or functional improvement — in a defined cohort of patients with a genetically confirmed recessive limb-girdle muscular dystrophy. The abstracts do not describe a trial design, a patient stratification strategy, or a funding source for such a trial. Without those, the gap between genetic knowledge and a proven treatment remains wide.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Seminars in Neurology · 2012 · 71 citations
The Muscular Dystrophies
AbstractThe muscular dystrophies are disorders of progressive muscular degeneration and weakness. As a group they display clinical heterogeneity that reflects the heterogeneity of molecular mechanisms responsible for them, and range from congenital to adulthood onset. Recent advances in the field include improved methods of diagnosis, continued identification of disease genes, and the development of a unified model of pathogenesis in facioscapulohumeral dystrophy. These advances are reflected in the development of new therapeutic approaches, some of which have already led to clinical trials in the dystrophinopathies and limb-girdle dystrophies.
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.
Frontiers in Pediatrics · 2021 · 4 citations · open access
Case Report: ISPD Gene Mutation Leads to Dystroglycanopathies: Genotypic Phenotype Analysis and Treatment Exploration
AbstractISPD gene mutation-related diseases have high clinical and genetic heterogeneity, and no studies have yet reported any effective treatments. We describe six patients with dystroglycanopathies caused by ISPD gene mutations and analyze their genotypes and phenotypes to explore possible effective treatments. Our results confirm that the phenotype of limb-girdle muscular dystrophies can be easily misdiagnosed as Duchenne muscular dystrophy and that exon deletions of ISPD gene are relatively common. Moreover, low-dose prednisone therapy can improve patients' exercise ability and prolong survival and may be a promising new avenue for ISPD therapy.
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.
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.
A patient with mutations in the dystrophin and the FKRP gene – „double trouble“ or incidental finding
AbstractAims: Becker muscular dystrophy (BMD) and limb girdle muscular dystrophy 2I (LGMD2I) are progressive neuromuscular disorders with a manifestation in childhood or adolescence. Both share proximal muscle weakness and high serum creatine kinase levels, possibly complicated by a cardiomyopathy. The clinical course can vary. BMD is an X-linked disease resulting from in-frame mutations/anomalies in the dystrophin gene whereas autosomal-recessive LGMD2I is caused by mutations in the fukutin-related protein gene (FKRP) leading to reduced O-glycosylation of α-dystroglycan.
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.
