DeCure for Autosomal recessive limb-girdle muscular dystrophy type 2I
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive limb-girdle muscular dystrophy type 2I — screening already-approved drugs against its 2-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 2I maps to a 2-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 2i 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
fukutin related protein (FKRP) — FKRP 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 cdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6KAJ · 2.2249 Å · ligand CYTIDINE-5'-DIPHOSPHATE (CDP). Experimental structure, not a prediction.
What the evidence adds up to
In 40 French patients with confirmed dysferlin protein deficiency and DYSF gene mutations, only half presented with the classic Miyoshi myopathy or limb-girdle muscular dystrophy type 2B. The remainder showed a proximodistal mixed phenotype (35%), pseudometabolic myopathy (10%), or asymptomatic hyperCKemia (5%). Disease could worsen rapidly, and a quarter of patients were initially misdiagnosed with polymyositis. The authors suggest a link between the proximodistal phenotype, inflammation, and severity. No curative treatment exists; steroids and immunosuppressants are not effective and carry side effects.
The gene for autosomal recessive limb-girdle muscular dystrophy type 2B was mapped to chromosome 2p in two large inbred families of different ethnic origin, with a maximum lod score of 3.57. Onset was in the pelvic girdle musculature in the late teens, with usually relatively slow progression. A rare homozygous duplication c.164dupA in DYSF was later reported in a Saudi patient, the first such case from that country with complete clinical, pathology, radiology, and genetic data.
Linkage to the seven known recessive LGMD loci was excluded in four large autosomal dominant limb-girdle pedigrees, underscoring the genetic heterogeneity of these disorders. Research into gene therapy for recessive muscular dystrophies is concentrating on complementation of defective genes with an extra copy, but no such therapy is available for dysferlinopathy.
What is still missing is a curative treatment, any large-scale natural history study that could power a trial, and a clear understanding of why the same DYSF mutation produces such variable phenotypes. Patient stratification by phenotype and inflammation status, and funding for a randomised controlled trial of any candidate therapy, remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 2007 · 265 citations
Phenotypic Study in 40 Patients With Dysferlin Gene Mutations
AbstractOBJECTIVE: To describe the phenotypic spectrum of dysferlin (DYSF) gene mutations (which cause dysferlinopathies, autosomal recessive muscular dystrophies) in patients with a dysferlin protein deficiency. DESIGN: Clinical, biological, and pathological data from 40 patients were reviewed. The diagnosis of dysferlinopathy was based on the absence or strong reduction of dysferlin in muscle, and confirmed by mutational screening of the DYSF gene. SETTING: Two French neuromuscular diseases centers (in Paris and Marseilles). RESULTS: Two main dysferlinopathy phenotypes are well recognized: Miyoshi myopathy and limb-girdle muscular dystrophy type 2B. Typical Miyoshi myopathy and limb-girdle muscular dystrophy type 2B were found in 20 (50%) patients only. Unusual phenotypes included a mixed phenotype, referred to as "proximodistal," combining distal and proximal onset in 14 (35%) patients, pseudometabolic myopathy in 4 (10%), and asymptomatic hyperCKemia (an increased serum creatine kinase level) in 2 (5%). The disease may worsen rapidly, and 10 (25%) patients were initially misdiagnosed as having polymyositis. We suggest a relationship between proximodistal phenotype, inflammation, and severity. CONCLUSION: In addition to typical Miyoshi myopathy and limb-girdle muscular dystrophy type 2B, dysferlinopathies are a clinically heterogeneous group of disorders ranging from asymptomatism to severe functional disability.
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.
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.
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.
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.
