DeCure for Autosomal dominant limb-girdle muscular dystrophy type 1G
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant limb-girdle muscular dystrophy type 1G — 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 dominant limb-girdle muscular dystrophy type 1G 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 dominant limb-girdle muscular dystrophy type 1g 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
heterogeneous nuclear ribonucleoprotein D like (HNRNPDL) — HNRNPDL 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 7ZIR · 2.5 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2021 case report describes six patients with dystroglycanopathies caused by ISPD gene mutations, a condition that includes limb-girdle muscular dystrophy phenotypes. The authors state that no studies had previously reported effective treatments for ISPD-related disease. In these six patients, low-dose prednisone therapy was associated with improved exercise ability and prolonged survival. The report does not give concrete numbers for survival or response rates, nor does it specify the dose or duration of treatment. The authors note that the phenotype can be easily misdiagnosed as Duchenne muscular dystrophy and that exon deletions of the ISPD gene are relatively common.
A 1998 study of four large families with autosomal dominant limb-girdle muscular dystrophy excluded linkage to all known dominant LGMD loci at that time, as well as to all seven recessive LGMD loci. This indicates that at least some dominant LGMD families carry mutations in genes that were then unidentified. A 2014 chapter on facioscapulohumeral muscular dystrophy, an unrelated autosomal dominant muscle disease, states that no effective therapeutic treatment is available for that condition.
The 2021 prednisone finding comes from a single small case series with no control group, no blinding, and no standardised outcome measures. The 1998 linkage exclusion confirms that dominant LGMD1G, if it is the same disorder as in those families, is genetically distinct from the loci tested. What is still missing is a prospective, controlled trial of prednisone or any other drug in a genetically confirmed LGMD1G cohort, along with funding for natural history studies and patient stratification by mutation type.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
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.
Oxford University Press eBooks · 2014 · 3 citations
Facioscapulohumeral muscular dystrophy
AbstractThis chapter is concerned with facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant inherited disorder with an estimated prevalence of 1 in 20 000 worldwide, making it the third most common hereditary muscle disease. FSHD is characterized by often asymmetric progressive weakness and wasting of muscles, usually starting in the face and shoulder girdle. In the majority of patients the disease is progressive, and muscles of the upper arms, foot extensors, and abdomen also become affected. Over time pelvic girdle, upper leg muscles, and eventually lower arm muscles may become weak. Approximately 20% of patients will become wheelchair dependent. Around 30% of gene carriers remain mildly or unaffected. The rate and extent of disease progression shows large interindividual variability. Currently there is no effective therapeutic treatment available. With all the recent progress in understanding the underlying pathogenic mechanism, it is hoped that rational therapeutic approaches will be developed.
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.
