DeCure for Nemaline myopathy 5C, autosomal dominant
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for nemaline myopathy 5C, autosomal dominant — 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 moduleNemaline myopathy 5C, autosomal dominant 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 nemaline myopathy 5c, 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.
What the evidence adds up to
Nemaline myopathies are a heterogeneous group of congenital myopathies caused by mutations in at least twelve genes, with ACTA1 and NEB being the most common. The condition is defined by rod-like or ovoid structures (nemaline bodies) visible on muscle biopsy, derived from Z lines. Their number and distribution do not correlate with severity or prognosis. Clinical presentation ranges from severe neonatal weakness and respiratory failure to a mild, slowly progressing proximal myopathy in childhood; adult-onset cases are usually autoimmune-related and progressive. In a series of 13 patients, two brothers died in the neonatal period from respiratory failure, and two infants who initially had moderate weakness later developed irreversible respiratory failure requiring continuous ventilation for 9 and 15 years. Among 143 cases from two centres, the authors examined prognostic risk factors and classification, but the abstract does not report specific survival or response rates.
Mutations in the NEB gene can cause fetal akinesia deformation sequence (FADS) and arthrogryposis multiplex congenita (AMC). In a study of seven cases from three families (Ashkenazi Jewish, Chinese, Korean), all were detected on prenatal ultrasound. Nemaline bodies were found in at least one case per family. In the Ashkenazi Jewish family, a known founder mutation was compounded by a recurrent novel splice site; in the other two families, only one pathogenic heterozygous mutation was detected. The authors state that NEB mutation is under-recognised as a cause of FADS/AMC and suggest it be included in genetic panels for these cases.
Current management of nemaline myopathy focuses on supportive treatment aimed at maintaining muscle strength, joint mobility, ambulation, respiration, and independence in daily activities. Animal models are advancing understanding of mutation effects and paving the way for future therapies, but no disease-modifying treatments are described in these abstracts. The 2013 review notes encouraging advances for the future but does not specify any drug or intervention.
What remains missing is any clinical trial testing a specific drug for nemaline myopathy, any identified molecular target for repurposing, and any validated biomarker or patient stratification strategy that could guide such a trial. Funding for natural history studies and for developing outcome measures in this ultra-rare, genetically heterogeneous population is also 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.
Journal of Muscle Research and Cell Motility · 2019 · 186 citations · open access
Nemaline myopathies: a current view
AbstractNemaline myopathies are a heterogenous group of congenital myopathies caused by de novo, dominantly or recessively inherited mutations in at least twelve genes. The genes encoding skeletal α-actin (ACTA1) and nebulin (NEB) are the commonest genetic cause. Most patients have congenital onset characterized by muscle weakness and hypotonia, but the spectrum of clinical phenotypes is broad, ranging from severe neonatal presentations to onset of a milder disorder in childhood. Most patients with adult onset have an autoimmune-related myopathy with a progressive course. The wide application of massively parallel sequencing methods is increasing the number of known causative genes and broadening the range of clinical phenotypes. Nemaline myopathies are identified by the presence of structures that are rod-like or ovoid in shape with electron microscopy, and with light microscopy stain red with the modified Gömöri trichrome technique. These rods or nemaline bodies are derived from Z lines (also known as Z discs or Z disks) and have a similar lattice structure and protein content. Their shape in patients with mutations in KLHL40 and LMOD3 is distinctive and can be useful for diagnosis. The number and distribution of nemaline bodies varies between fibres and different muscles but does not correlate with severity or prognosis. Additional pathological features such as caps, cores and fibre type disproportion are associated with the same genes as those known to cause the presence of rods. Animal models are advancing the understanding of the effects of various mutations in different genes and paving the way for the development of therapies, which at present only manage symptoms and are aimed at maintaining muscle strength, joint mobility, ambulation, respiration and independence in the activities of daily living.
Current Opinion in Neurology · 2013 · 82 citations
Recent advances in nemaline myopathy
AbstractPURPOSE OF REVIEW: This article reviews recent advances in the understanding of nemaline myopathy, with a focus on the genetic basis of the disorder, histology, and pathogenesis. RECENT FINDINGS: Pathogenic mutations have been identified in eight genes and there is evidence of further genetic heterogeneity in nemaline myopathy. Clinical presentation, histological features on skeletal muscle biopsy, and pattern of changes on muscle MRI may guide prioritization of molecular genetic testing. It is anticipated that use of new technologies such as whole exome sequencing and comparative genomic hybridization will increase the number of genes associated with nemaline myopathy and the proportion of patients in whom the genetic basis of the disorder is identified. Single fiber studies and animal models continue to add to understanding of the pathogenesis of this disorder. Current management focuses on supportive treatment; however, encouraging advances are emerging for the future. SUMMARY: Recent advances in understanding of nemaline myopathy have important implications for clinical practice and for genetic diagnosis of patients with nemaline myopathy.
AbstractThe marked heterogeneity of nemaline myopathy is again shown in the present series of 13 patients. Most children have a long-standing, mild, and slowly progressing proximal myopathy. Two brothers with extreme weakness died during the neonatal period of respiratory failure representing the X-linked variant. One adult with proximal weakness was also diagnosed as having nemaline myopathy. An unusual course was observed in 2 infants who initially had moderate weakness but subsequently developed severe generalized weakness including respiratory muscles. This led to irreversible respiratory failure requiring continuous ventilatory support for as long as 9 and 15 years, respectively. Although uncommon, the possibility of an imminent respiratory failure in initially weak infants should also be taken into account within the clinical spectrum of nemaline myopathy.
Galter Health Sciences Library, Northwestern University · 2001 · 0 citations · open access
Nemaline Myopathy: Clinical Study
AbstractClinical and genetic characteristics, prognostic risk factors, and classification of nemaline myopathy (NM) are examined in a study of 143 cases identified at two centers in Australia and North America and reported from the Neurogenetics Research Unit, University of Sydney, Australia; Childrens Hospital, Boston; and other centers.
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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