DeCure for Congenital merosin-deficient muscular dystrophy 1A
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital merosin-deficient muscular dystrophy 1A — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongenital merosin-deficient muscular dystrophy 1A maps to a 3-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 merosin-deficient muscular dystrophy 1a 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
laminin subunit alpha 2 (LAMA2) — LAMA2 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 4YEQ · 3.2 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is caused by mutation of the laminin alpha-2 gene (LAMA2) on chromosome 6q22-23. It affects around 1-9 per 1,000,000 individuals. Diagnosis rests on severe congenital hypotonia, weakness, elevated serum creatine kinase, white matter abnormalities on MRI, and negative immunostaining for merosin in muscle biopsy. One case report describes a girl with serum creatine kinase of 1045 U/L, absent merosin on immunohistochemistry, normal dystrophin and utrophin expression, and MRI showing diffuse hyperintensity in white matter, hypotrophy of the corpus callosum, and a reduced pituitary size. Another report notes congenital foot deformity in association with the condition.
Two Chinese patients are described with specific LAMA2 mutations. Patient 1 had a double mutation c.[9101_9104dupAACA:3412G>A] p.[H3035QfsX4:V1138M]; her parents and a sibling were heterozygous carriers. Patient 2 had a novel homozygous nonsense mutation c.2907C>A (p.Cys969X) in exon 21. Both showed typical clinical symptoms and complete absence of laminin alpha2 chain around muscle fibres on immunohistochemistry, with dystrophic changes and proliferated fibrotic tissue in skeletal muscle.
There is no curative therapy. The available approach is control and prevention of complications. One case report describes a patient with compound heterozygosity mutation and global psychomotor development delay receiving multidisciplinary rehabilitation treatment. No drug treatment, no clinical trial, and no repurposing candidate are reported in these abstracts. What is missing is any evidence for pharmacological intervention, any trial design, any patient stratification strategy, and any funding directed toward drug development for MDC1A.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Definitions · 2020 · 9 citations · open access
Merosin-Deficient Congenital Muscular Dystrophy Type 1A
AbstractMerosin-deficient congenital muscular dystrophy type 1A (MDC1A) is the most common form of congenital muscular dystrophy. MDC1A is caused by mutation of the laminin alpha-2 gene (LAMA2), localized to chromosome 6q22-23. The diagnosis of merosin-deficient CMD is based on the clinical findings of severe congenital hypotonia, weakness, with high blood levels of creatine kinase, WM abnormalities, and dystrophy associated with negative immunostaining of biopsied muscle for merosin. We investigated clinical and laboratory a patient: a girl with merosin-deficient congenital muscular dystrophy type 1A. Clinically the particularity of the case is the association of merosin-negative congenital muscular dystrophy (MN-CMD) with congenital feet deformity. The level of serum creatine kinase is elevated 1045 U/L. Immunohistochemistry show presence of dystrophin, lack of merosin, also the utrophin is normally expressed. Nerve conduction studies are normally, while electromyography suggested a myopathic process with early recruitment and decreased amplitude and duration of response. Magnetic resonance imaging: MRI T1 and MRI T2 show hypointensity and diffuse hyperintensity respectively in the white matter. Supratentorial MRI images showed hypotrophy of the corpus callosum and almost absent cingulate gyrus. In addition, hypophysis is reduced size.
Congenital Muscular Dystrophy Type 1A: The Role of Multidisciplinary Rehabilitation
AbstractMerosinopathy is a subtype of muscular dystrophy with recessive autosomal transmission, resulting from an α2-chain-laminin/merosin deficiency. It affects around 1-9/ 1 000 000 individuals. Classically, it is subdivided in two phenotypic categories: one that is more common and severe, known as congenital muscular dystrophy type 1A, and a lesser common form of mild presentation. Congenital muscular dystrophy type 1A presents early with severe neonatal hypotonia and inability to stand and walk. Dysphagia, respiratory failure and scoliosis may also occur. There is no curative therapy, thereby the control and prevention of complications are the available approach. The authors present a case report of a congenital muscular dystrophy type 1A patient with a compound heterozygosity mutation presenting a global psychomotor development delay under multidisciplinary rehabilitation treatment.
El federalismo alemán y "el movimiento necesario de las cosas"
AbstractWe report a family and a single patient in China involved with merosin-deficient congenital muscular dystrophy (MDC1A) with typical clinical symptoms. Pathological analysis of biopsied skeletal muscle showed dystrophic changes with proliferated fibrotic tissue elements as the predominant finding. Immunohistochemical analysis demonstrated the complete absence of the laminin alpha2 chain (merosin) around muscle fibers. In patient 1, a double mutation, c.[9101_9104dupAACA:3412G>A] p.[H3035QfsX4:V1138M] was detected, whereas her parents and another sibling were heterozygous carriers. Patient 2 had a novel homozygous nonsense mutation, c.2907C>A (p.Cys969X), in exon 21. The genotype-phenotype correlation of Chinese children with novel merosin-deficient congenital muscular dystrophy is reported.
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.
