DeCure for Muscular dystrophy, limb-girdle, autosomal recessive 28
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy, limb-girdle, autosomal recessive 28 — 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 moduleMuscular dystrophy, limb-girdle, autosomal recessive 28 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 muscular dystrophy, limb-girdle, autosomal recessive 28 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
3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) — HMGCR 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 coadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1DQA · 2.0 Å · ligand COENZYME A (COA). Experimental structure, not a prediction.
What the evidence adds up to
Limb-girdle muscular dystrophy autosomal recessive 28 (LGMDR28) is not mentioned by name in any of the provided abstracts. The abstracts cover the broader category of limb-girdle muscular dystrophies (LGMDs), which are described as a clinically and genetically heterogeneous group of disorders of progressive muscular degeneration and weakness, ranging from congenital to adulthood onset. As of a 2023 update, 31 LGMD subtypes are described, 26 of them autosomal recessive. The same update notes recent therapeutic advances and the development of new therapeutic approaches, some of which have already led to clinical trials in the limb-girdle dystrophies. No specific drug, trial result, or outcome data for any LGMD subtype is given in these abstracts.
One abstract reports a 63-year-old patient with LGMDR8 (TRIM32-related LGMD) who went undiagnosed for 24 years. That patient carried two TRIM32 missense variants, one classified as a variant of uncertain significance and the other as likely pathogenic. A literature review identified 53 LGMDR8 patients reported in 20 papers, carrying 26 different TRIM32 variants. No treatment or outcome data is provided for these patients. Another abstract describes a single Saudi patient with limb-girdle muscular dystrophy type 2B (dysferlinopathy) carrying a rare homozygous duplication in DYSF. The abstract states there is no curative treatment and that steroids and immunosuppressive medications are not effective and may have several side effects.
A 1989 estimate suggested that 2.5–4% of male isolated patients diagnosed as Duchenne muscular dystrophy may have an autosomal recessive form, which could explain inconsistencies between clinical diagnosis and dystrophin assessment. A 1998 study of four dominant LGMD families excluded linkage to all known dominant and seven recessive LGMD loci at that time, underscoring the genetic heterogeneity. What remains missing for LGMDR28 specifically are any published clinical trials, any tested drugs, any patient outcome data, and even a confirmed molecular diagnosis or gene assignment for that subtype. The field still lacks funded trials, validated biomarkers, and patient stratification strategies for most individual LGMD subtypes.
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.
American Journal of Medical Genetics · 1989 · 45 citations
Estimate of the proportion of Duchenne muscular dystrophy with autosomal recessive inheritance
AbstractThe aim of the present report was to estimate the proportion of autosomal recessive (AR) inheritance among families with affected males diagnosed as Duchenne muscular dystrophy (DMD) in which X-linked inheritance could not be confirmed. A total of 470 families was studied: 20 with at least one affected girl with "Duchenne-like" phenotype and 450 with only affected boys. Based on the number of families with at least one affected girl and the number of patients per sibship among these pedigrees, the proportion of families with DMD inherited as an AR trait was estimated at 6.8%. It is also estimated that 2.5-4% of male isolated patients diagnosed as DMD may have the AR form, which could be one possible explanation for the inconsistent results between clinical diagnosis and dystrophin assessment in one case recently reported.
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.
Frontiers in Neurology · 2024 · 2 citations · open access
Case report: A novel patient presenting TRIM32-related limb-girdle muscular dystrophy
AbstractLimb-girdle muscular dystrophy autosomal recessive 8 (LGMDR8) is a rare clinical manifestation caused by the presence of biallelic variants in the TRIM32 gene. We present the clinical, molecular, histopathological, and muscle magnetic resonance findings of a novel 63-years-old LGMDR8 patient of Italian origins, who went undiagnosed for 24 years. Clinical exome sequencing identified two TRIM32 missense variants, c.1181G > A p.(Arg394His) and c.1781G > A p.(Ser594Asp), located in the NHL1 and NHL4 structural domains, respectively, of the TRIM32 protein. We conducted a literature review of the clinical and instrumental data associated to the so far known 26 TRIM32 variants, carried biallelically by 53 LGMDR8 patients reported to date in 20 papers. Our proband's variants were previously identified only in three independent LGMDR8 patients in homozygosis, therefore our case is the first in literature to be described as compound heterozygous for such variants. Our report also provides additional data in support of their pathogenicity, since p.(Arg394His) is currently classified as a variant of uncertain significance, while p.(Ser594Asp) as likely pathogenic. Taken together, these findings might be useful to improve both the genetic counseling and the diagnostic accuracy of this rare neuromuscular condition.
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.
