DeCure for Muscular dystrophy, limb-girdle, autosomal dominant
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for muscular dystrophy, limb-girdle, autosomal dominant — screening already-approved drugs against its 4-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 dominant maps to a 4-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 dominant 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
transportin 3 (TNPO3) — TNPO3 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 bcndrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6GX9 · 2.7 Å · ligand BICINE (BCN). Experimental structure, not a prediction.
What the evidence adds up to
Limb-girdle muscular dystrophy is a class of disorders defined by progressive proximal muscle weakness and dystrophic changes on pathology. As of 2023, thirty-one LGMD subtypes are described, five of which are autosomal dominant and 26 autosomal recessive. The autosomal dominant forms are the focus here.
A 1991 report describes a patient with autosomal dominant LGMD, with affected individuals in both sexes across four generations. Symptoms appeared in adulthood, with pelvic-femoral weakness preceding scapulo-humeral involvement. Clinical expressivity was variable but described as benign, with no reduction in life expectancy. Muscle biopsy showed myopathic changes with vacuoles. The authors note at least five other genealogies in the literature with similar clinical and pathological features.
A 2008 case report describes a 56-year-old man with a late-onset autosomal dominant LGMD, with expression limited to males. Muscle biopsy of a clinically less affected muscle showed only minor changes by light microscopy except for variation in type II fibre diameter. Electron microscopy revealed extensive damage to type II fibres. The 2001 review covers the molecular genetics, clinical features, and diagnostic issues for each primary genetic cause of LGMD, but does not provide survival or response rate data for any specific form.
No controlled trials, no quantitative efficacy data, and no specific drug interventions are reported in these abstracts. What is missing is any trial design, any patient stratification by the specific dominant gene involved, and any funding for clinical studies in this rare subgroup.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 1988 · 125 citations
Clinical and genetic investigation in autosomal dominant limb‐girdle muscular dystrophy
AbstractLimb-girdle muscular dystrophy is a syndrome of progressive myopathic weakness affecting shoulder and hip girdle and proximal arm and leg muscles. The disease occurs either sporadically or inherited as an autosomal recessive trait. Autosomal dominant inheritance is rare. We report a large family with apparent autosomal dominant inheritance. Sixteen members were affected with a disease characterized by proximal weakness, leg greater than arm, onset in the third decade, elevated CK and CK MB levels, and myopathic EMGs and muscle biopsies. Linkage analysis revealed no conclusive linkage.
Current Opinion in Neurology · 2001 · 22 citations
The ABCʼs of limb-girdle muscular dystrophy: α-sarcoglycanopathy, Bethlem myopathy, calpainopathy and more
AbstractLimb-girdle muscular dystrophy is a class of disorders encompassing many forms of this disease. Variation exists between the inheritance patterns, genes responsible, course of disease and symptoms, with the cohesive factor among these disorders being the predominance of proximal muscle weakness. Here we review each form of limb-girdle muscular dystrophy with attention to molecular genetics, clinical features, inheritance, and diagnostic issues pertaining to each primary genetic cause.
A Late Autosomal Dominant Form of Limb-Girdle Muscular Dystrophy
AbstractA case report of a 56-year-old man with a late-onset limb-girdle muscular dystrophy is presented. The disease was caused by an autosomal dominant gene with expression limited to males. A muscle biopsy was performed in a clinically less affected limb-girdle muscle. Light microscopic and histochemical examination showed only minor changes with the exception of important variation in the diameter of the type II muscle fibers. With the electron microscope a large variety of alterations, as well as extensive damage to type II fibers, were seen. The genetic and morphological findings are discussed in relation to the classification and etiology of the limb-girdle muscular dystrophy.
Limb girdle muscular dystrophy with autosomal dominant inheritance
AbstractWe describe a patient suffering from limb-girdle muscular dystrophy with autosomal dominant inheritance proved by the presence of other similar cases in both sexes scattered over 4 generations of his family tree. In all patients the symptoms appeared in adult age and pelvi-femoral preceded scapulo-humeral involvement. Clinical expressivity has been variable, but rather benign without any reduction in life expectancy. Myopathic changes with vacuoles were present in muscle on light and electron microscopic examination. In the literature we found at least another 5 genealogies with autosomal dominant LGMD which had similar clinical and pathological features to those of our patient.
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.
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.
