DeCure for Congenital muscular dystrophy due to LMNA mutation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital muscular dystrophy due to LMNA mutation — 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 moduleCongenital muscular dystrophy due to LMNA mutation 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 congenital muscular dystrophy due to lmna mutation 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
lamin A/C (LMNA) — LMNA 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 6JLB · 3.205 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 50 patients from the United States and Canada, 15 novel LMNA mutations were identified, including eight missense mutations, three splice site mutations, one duplication, one deletion, and two silent mutations. The study reported that two mutations, p.R249W/Q and p.E358K, were associated with an early onset Emery-Dreifuss muscular dystrophy phenotype and had recently been linked to LMNA-associated congenital muscular dystrophy (L-CMD). Analysis of four lamin A mutations showed that some caused nuclear deformations and lamin B redistribution in a mutation-specific manner. No treatment or intervention was tested.
Two unrelated children with L-CMD presented with a dropped head syndrome. One carried a novel L35P mutation, the other a previously reported R249W mutation. The authors noted that recognising the phenotype can spare patients unnecessary procedures and should prompt monitoring for cardiac arrhythmias, but no therapeutic data were provided.
In a Japanese girl with L-CMD, a novel heterozygous missense mutation, c.115A>C (p.Asn39His), was identified using a targeted gene panel for muscle diseases. No treatment or outcome data were reported.
Among 42 Russian probands with congenital muscular dystrophy, the frequency of LMNA mutations was at least 12%. A major mutation, c.94_96delAAC, was described. The phenotype included progressive flaccid paralysis with predominant involvement of axial muscles and plantar flexors of the foot. No intervention was studied.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Mutation · 2010 · 73 citations
Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations
AbstractMutations in LMNA cause a variety of diseases affecting striated muscle including autosomal Emery-Dreifuss muscular dystrophy (EDMD), LMNA-associated congenital muscular dystrophy (L-CMD), and limb-girdle muscular dystrophy type 1B (LGMD1B). Here, we describe novel and recurrent LMNA mutations identified in 50 patients from the United States and Canada, which is the first report of the distribution of LMNA mutations from a large cohort outside Europe. This augments the number of LMNA mutations known to cause EDMD by 16.5%, equating to an increase of 5.9% in the total known LMNA mutations. Eight patients presented with either p.R249W/Q or p.E358K mutations and an early onset EDMD phenotype: two mutations recently associated with L-CMD. Importantly, 15 mutations are novel and include eight missense mutations (p.R189P, p.F206L, p.S268P, p.S295P, p.E361K, p.G449D, p.L454P, and p.W467R), three splice site mutations (c.IVS4 + 1G>A, c.IVS6 - 2A>G, and c.IVS8 + 1G>A), one duplication/in frame insertion (p.R190dup), one deletion (p.Q355del), and two silent mutations (p.R119R and p.K270K). Analysis of 4 of our lamin A mutations showed that some caused nuclear deformations and lamin B redistribution in a mutation specific manner. Together, this study significantly augments the number of EDMD patients on the database and describes 15 novel mutations that underlie EDMD, which will contribute to establishing genotype-phenotype correlations.
Two children with “dropped head” syndrome due to lamin A/C mutations
AbstractLMNA-related congenital muscular dystrophy (L-CMD) is a recently described disorder characterized by infantile-onset myopathy due to mutations in the lamin A/C (LMNA) gene. We report the genetic and clinical characteristics of two unrelated L-CMD patients. Patient 1 harbored a novel, L35P mutation and patient 2 a previously reported R249W mutation. The striking phenotype associated with L-CMD is important to recognize, as molecular diagnostic testing can spare patients unnecessary procedures and prompt the physician to monitor for associated cardiac arrhythmias.
Human Genome Variation · 2018 · 7 citations · open access
A novel LMNA mutation identified in a Japanese patient with LMNA-associated congenital muscular dystrophy
AbstractAbstract LMNA-associated congenital muscular dystrophy (L-CMD) is a severe form of muscle laminopathy. LMNA encodes lamin A, which an intermediate filament protein that attaches to the inner membrane of the nuclear envelope. We performed sequence analysis based on our original targeted gene panel system for muscle diseases to obtain a molecular diagnosis in a Japanese girl with L-CMD. A novel heterozygous missense mutation, c.115A>C (p.Asn39His), in LMNA is reported.
Is the Next Generation Sequencing the Essential Tool for the Early Diagnostic Approach in Congenital Muscular Dystrophy? New Mutation in the Gen LMNA Associated with Serious Phenotype
AbstractBACKGROUND: Laminopathies are a group of diseases caused by mutations in the LMNA gene. Congenital dystrophy of the LMN is a rare disease, with less than 100 cases described in the literature. OBJECTIVES AND MATERIALS AND METHODS: We present the clinical case of a patient with congenital muscular dystrophy associated with an undescribed mutation in the LMNA gene. RESULTS: The patient presented progressive motor delay from 10 months with a physical examination consisting of global hypotonia, bilateral winged scapula, areflexia, hip and knee flexion posture, and positive Gowers. The patient developed progressive weakness with neck tone loss, functional impairment, and loss of gait at 5 years. CONCLUSIONS: To date, more than 20 mutations associated with congenital LMNA muscular dystrophy have been identified, most due to a single amino acid change (aa), few due to the gain or loss of several aa as in our patient.
S S Korsakov Journal of Neurology and Psychiatry · 2016 · 0 citations
Clinical/genetic characteristics of patients with congenital muscular dystrophy caused by mutations in the LMNA gene
AbstractOBJECTIVE: To study clinical/genetic characteristics of congenital muscular dystrophy caused by mutations in the LMNA gene in 5 patients from the Russian population. MATERIAL AND METHODS: DNA samples of 42 probands, aged from 2 months to 9 years, with characteristic signs of congenital muscular dystrophy from nonrelated families were studied. The diagnosis was based on the results of genealogical analysis, neurological examination, serum creatine phosphokinase activity, results of electroneuromyography. RESULTS AND CONCLUSION: In the Russian population, the frequency of congenital muscular dystrophy caused by mutations in the LMNA gene is not less than 12% of all cases of this group of diseases. The results indicate the presence of major mutation c.94_96delAAC in the LMNA gene. Specific phenotypic features of this form of congenital muscular dystrophy with symptoms of progressive flaccid paralysis with predominant lesions of axial muscles and plantar flexor muscles of the foot are described.
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.
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