DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for myopathy, centronuclear, 5 — 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 moduleMyopathy, centronuclear, 5 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 myopathy, centronuclear, 5 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
cytochrome P450 family 1 subfamily B member 1 (CYP1B1) — CYP1B1 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…
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RCSB Protein Data Bank · entry 3PM0 · 2.7 Å · ligand PROTOPORPHYRIN IX CONTAINING FE (HEM). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 review states that centronuclear myopathy (CNM) is an inherited neuromuscular disorder with centrally placed nuclei on muscle biopsy. The X-linked form (myotubular myopathy) has an estimated incidence of 2 per 100,000 male births; epidemiological data for other forms are not available. The X-linked form usually presents at birth with marked weakness, hypotonia, external ophthalmoplegia, and respiratory failure; affected infants are often macrosomic with length above the 90th centile. A 1977 report describes a severe neonatal form with respiratory muscle involvement that progresses rapidly and is fatal before three years of age. The same report notes that in a majority of cases the disease is either moderately severe or mild, with affected individuals confined to a wheelchair by adolescence or early adult life.
Mutations in the myotubularin (MTM1) gene on chromosome Xq28 have been identified in most patients with the X-linked recessive form. Autosomal-dominant and autosomal-recessive forms have been associated with mutations in the dynamin 2 (DNM2) gene and the amphiphysin 2 (BIN1) gene, respectively. Single cases have been linked to mutations in the ryanodine receptor (RYR1) and hJUMPY (MTMR14) genes. A 2019 mouse study found that BIN1 expression rescued integrin and laminin alterations and restored myofiber integrity in mice with defects in myofiber shape and size, supporting the idea that MTM1 and BIN1 are functionally linked and necessary for focal adhesions in skeletal muscle. The authors suggested that BIN1 modulation might be an effective strategy for treating X-linked centronuclear myopathy (XLCNM).
Management of CNM is mainly supportive, based on a multidisciplinary approach. The X-linked form due to MTM1 mutations is often fatal in infancy, while dominant forms due to DNM2 mutations and some cases of the recessive BIN1-related form appear to have a more favourable prognosis. A 1995 case report describes a 12-year-old girl who developed a rare myopathy associated with epsilon-aminocaproic acid, which resolved when the drug was discontinued; this is not a treatment for CNM. A 2008 case report notes that central nuclei may be a non-specific change in several conditions, and that centronuclear myopathy could turn out to be a syndrome from which different entities can be isolated.
What is still missing is a therapy that alters the natural history of any form of CNM in humans. The BIN1 modulation strategy has only been tested in mice. No clinical trial has been conducted. Patient stratification by genotype is incomplete, and the natural history of the autosomal forms remains poorly quantified. Funding for preclinical work and for the development of outcome measures suitable for a rare, heterogeneous disease is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science Translational Medicine · 2019 · 54 citations
Amphiphysin 2 modulation rescues myotubular myopathy and prevents focal adhesion defects in mice
Abstractmice were associated with defects in myofiber shape and size. BIN1 expression rescued integrin and laminin alterations and restored myofiber integrity, supporting the idea that MTM1 and BIN1 are functionally linked and necessary for focal adhesions in skeletal muscle. The results suggest that BIN1 modulation might be an effective strategy for treating XLCNM.
Centronuclear Myopathy in the Newborn Period Causing Severe Respiratory Distress
AbstractCentronuclear myopathy can be classified into four clinical varieties based on age, severity at onset, and rapidity of progress. In the severe form with involvement of respiratory muscles at birth, the progress is rapid and fatal before 3 years of age. The case described in this report illustrates rapid progression of muscle paralysis and death in a neonate. However, in a majority of cases the disease is either moderately severe or mild with the affected individuals confined to wheel chair by adolescence or early adult life. Diagnosis of the disease is based on appropriate muscle histopathology and electron microscopic studies.
Journal of Pediatric Hematology/Oncology · 1995 · 12 citations
ϵ-Aminocaproic Acid-Associated Myopathy in a Child
AbstractPURPOSE: A 12-year-old girl developed severe autoimmune thrombocytopenia after a bone marrow transplant for acute lymphoblastic leukemia. RESULTS: Although epsilon-aminocaproic acid helped to control her bleeding, it eventually caused a rare myopathy previously undescribed in a pediatric patient. CONCLUSION: The myopathy resolved when the drug was discontinued and a different antifibrinolytic agent was used.
Histochemical and Ultrastructural Findings in a Case of Centronuclear Myopathy
AbstractA case of centronuclear myopathy is presented. The presence of central nuclei in almost all fibres, the existence of type I fibres only, the histochemical pattern of a negative central zone with a perinuclear halo and a hyperactive rim with oxidative enzymes and the ultrastructural data are discussed in the light of the previous literature. The possible relationships with other myopathies are taken into consideration as well as the fact that central nuclei may be a non-specific change in several conditions. Consequently centronuclear myopathy could turn out to be a syndrome from which different entities can be isolated.
AbstractCentronuclear myopathy (CNM) is an inherited neuromuscular disorder characterised by clinical features of a congenital myopathy and centrally placed nuclei on muscle biopsy.The incidence of X-linked myotubular myopathy is estimated at 2/100000 male births but epidemiological data for other forms are not currently available.The clinical picture is highly variable. The X-linked form usually gives rise to a severe phenotype in males presenting at birth with marked weakness and hypotonia, external ophthalmoplegia and respiratory failure. Signs of antenatal onset comprise reduced foetal movements, polyhydramnios and thinning of the ribs on chest radiographs; birth asphyxia may be the present. Affected infants are often macrosomic, with length above the 90th centile and large head circumference. Testes are frequently undescended. Both autosomal-recessive (AR) and autosomal-dominant (AD) forms differ from the X-linked form regarding age at onset, severity, clinical characteristics and prognosis. In general, AD forms have a later onset and milder course than the X-linked form, and the AR form is intermediate in both respects.Mutations in the myotubularin (MTM1) gene on chromosome Xq28 have been identified in the majority of patients with the X-linked recessive form, whilst AD and AR forms have been associated with mutations in the dynamin 2 (DNM2) gene on chromosome 19p13.2 and the amphiphysin 2 (BIN1) gene on chromosome 2q14, respectively. Single cases with features of CNM have been associated with mutations in the skeletal muscle ryanodine receptor (RYR1) and the hJUMPY (MTMR14) genes.Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features; muscle magnetic resonance imaging may complement clinical assessment and inform genetic testing in cases with equivocal features. Genetic counselling should be offered to all patients and families in whom a diagnosis of CNM has been made.The main differential diagnoses include congenital myotonic dystrophy and other conditions with severe neonatal hypotonia.Management of CNM is mainly supportive, based on a multidisciplinary approach. Whereas the X-linked form due to MTM1 mutations is often fatal in infancy, dominant forms due to DNM2 mutations and some cases of the recessive BIN1-related form appear to be associated with an overall more favourable prognosis.
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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