DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for MYH7-related skeletal myopathy — 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 moduleMYH7-related skeletal myopathy 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 myh7-related skeletal myopathy 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
myosin heavy chain 7 (MYH7) — MYH7 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9TPJ · 3.02 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
MYH7-related skeletal myopathy is a genetic disorder caused by mutations in the MYH7 gene, which encodes the slow skeletal muscle fibre myosin heavy chain. A 2014 study of four affected members across three generations of one family identified a novel heterozygous missense mutation, p.Leu1723Pro, in the myosin tail domain. Symptoms began in early childhood with mild delayed motor development, later progressing to tibialis anterior weakness, calf hypertrophy, and significant weakness of the quadriceps. No cardiac or ocular involvement was noted. Muscle biopsies showed eccentric cores in type 1 fibres with abrupt borders, and electron microscopy confirmed both unstructured and structured cores. The study described MYH7 as an additional causative gene for autosomal dominant central core disease.
A 2020 report on eight affected family members from four new families with Laing distal myopathy expanded the clinical and genetic spectrum. Two families carried novel MYH7 mutations (Y162D and A1438P), one had dual mutations (V39M and K1617del), and one family with the E1508del mutation showed severe early-onset weakness with contractures, respiratory insufficiency, and dilated cardiomyopathy. The classic Laing distal myopathy phenotype includes early-onset foot dorsiflexor and great toe extensor weakness, followed by neck flexor and finger extensor weakness, but the report noted that the spectrum now includes congenital myopathies, late-onset myopathies, myosin storage myopathy, and scapuloperoneal myopathies.
A 2022 study described two unrelated boys, aged 9 and 3.5 years, both carrying the same in-frame deletion in the MYH7 head domain (p.Glu500del). Both presented with prenatal polyhydramnios, congenital axial stiffness, and muscular hypertonus, with no cardiac involvement. In one patient the phenotype evolved into an axial/proximal skeletal myopathy without distal involvement or cardiomyopathy, while the other exhibited predominantly stiffness and respiratory involvement. The mutation occurred de novo in one patient, while mosaicism was detected in the blood of the father of the second patient. The study noted that most MYH7-related skeletal myopathies are caused by variants in the rod domain and result in distal muscle weakness, whereas these head-domain mutations produced an unusual axial stiffness phenotype.
What is still missing are large, prospective natural history studies to define the full phenotypic range and progression of MYH7-related skeletal myopathy, given the small sample sizes and retrospective nature of all current reports. There are no clinical trials testing any intervention, and no validated outcome measures for this specific population. Patient stratification by mutation location (head versus rod domain) and by presence or absence of cardiac involvement will be necessary for any future trial design. Funding for such studies remains limited, as the condition is extremely rare.
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 Neurology Neurosurgery & Psychiatry · 2014 · 26 citations · open access
Autosomal dominant eccentric core disease caused by a heterozygous mutation in the<i>MYH7</i>gene
AbstractBACKGROUND: Autosomal dominant (AD) central core disease (CCD) is a congenital myopathy characterised by the presence of cores in the muscle fibres which correspond to broad areas of myofibrils disorganisation, Z-line streaming and lack of mitochondria. Heterozygous mutations in the RYR1 gene were observed in the large majority of AD-CCD families; however, this gene was excluded in some of AD-CCD families. OBJECTIVE: To enlarge the genetic spectrum of AD-CCD demonstrating mutations in an additional gene. PATIENTS AND METHODS: Four affected AD family members over three generations, three of whom were alive and participate in the study: the mother and two of three siblings. The symptoms began during the early childhood with mild delayed motor development. Later they developed mainly tibialis anterior weakness, hypertrophy of calves and significant weakness (amyotrophic) of quadriceps. No cardiac or ocular involvement was noted. RESULTS: The muscle biopsies sections showed a particular pattern: eccentric cores in type 1 fibres, associated with type 1 predominance. Most cores have abrupt borders. Electron microscopy confirmed the presence of both unstructured and structured cores. Exome sequencing analysis identified a novel heterozygous missense mutation p.Leu1723Pro in MYH7 segregating with the disease and affecting a conserved residue in the myosin tail domain. CONCLUSIONS: We describe MYH7 as an additional causative gene for AD-CCD. These findings have important implications for diagnosis and future investigations of AD-congenital myopathies with cores, without cardiomyopathy, but presenting a particular involvement of distal and quadriceps muscles.
Journal of Clinical Neuromuscular Disease · 2020 · 3 citations
Laing Myopathy: Report of 4 New Families With Novel MYH7 Mutations, Double Mutations, and Severe Phenotype
AbstractLaing distal myopathy (LDM) is an autosomal dominant disorder caused by mutations in the slow skeletal muscle fiber myosin heavy chain (MYH7) gene on chromosome 14q11.2. The classic LDM phenotype-including early-onset, initial involvement of foot dorsiflexors and great toe extensors, followed by weakness of neck flexors and finger extensors-is well documented. Since the original report by Laing et al in 1995, the spectrum of MYH7-related myopathies has expanded to include congenital myopathies, late-onset myopathies, myosin storage myopathy, and scapuloperoneal myopathies. Most patients with LDM harbor mutations in the midrod domain of the MYH7 gene, but rare cases document disease-associated mutations in the globular head region. In this report, we add to the medical literature by describing the clinicopathological findings in 8 affected family members from 4 new LDM families-including 2 with novel MYH7 mutations (Y162D and A1438P), one with dual mutations (V39M and K1617del), and one family (E1508del) with severe early-onset weakness associated with contractures, respiratory insufficiency, and dilated cardiomyopathy. Our families highlight the ever-expanding clinical spectrum and genetic variation of the skeletal myopathies related to MYH7 gene mutations.
Orphanet Journal of Rare Diseases · 2022 · 2 citations · open access
A recurrent single-amino acid deletion (p.Glu500del) in the head domain of ß-cardiac myosin in two unrelated boys presenting with polyhydramnios, congenital axial stiffness and skeletal myopathy
AbstractBACKGROUND: Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in the MYH7 gene are predicted to alter the rod domain of the of ß-cardiac myosin molecule, resulting in distal muscle weakness as the predominant manifestation. Here we describe two unrelated patients harboring an in-frame deletion in the MYH7 gene that is predicted to result in deletion of a single amino acid (p.Glu500del) in the head domain of ß-cardiac myosin. Both patients display an unusual skeletal myopathy phenotype with congenital axial stiffness and muscular hypertonus, but no cardiac involvement. RESULTS: Clinical data, MRI results and histopathological data were collected retrospectively in two unrelated boys (9 and 3.5 years old). Exome sequencing uncovered the same 3-bp in-frame deletion in exon 15 (c.1498_1500delGAG) of the MYH7 gene of both patients, a mutation which deletes a highly conserved glutamate residue (p.Glu500del) in the relay loop of the head domain of the ß-cardiac myosin heavy chain. The mutation occurred de novo in one patient, whereas mosaicism was detected in blood of the father of the second patient. Both boys presented with an unusual phenotype of prenatal polyhydramnios, congenital axial stiffness and muscular hypertonus. In one patient the phenotype evolved into an axial/proximal skeletal myopathy without distal involvement or cardiomyopathy, whereas the other patient exhibited predominantly stiffness and respiratory involvement. We review and compare all patients described in the literature who possess a variant predicted to alter the p.Glu500 residue in the ß-cardiac myosin head domain, and we provide in-silico analyses of potential effects on polypeptide function. CONCLUSION: The data presented here expand the phenotypic spectrum of mutations in the MYH7 gene and have implications for future diagnostics and therapeutic approaches.
MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients
AbstractAbstract Background Myosin heavy chain 7 (MYH7)-related myopathies are emerging as an important group of muscle diseases of childhood and adulthood, with variable clinical and histopathological expression depending on the type and location of the mutation. Mutations in the head and neck domains are a well-established cause of hypertrophic cardiomyopathy whereas mutation in the distal regions have been associated with a range of skeletal myopathies with or without cardiac involvement, including Laing distal myopathy and Myosin storage myopathy. Recently the spectrum of clinical phenotypes associated with mutations in MYH7 has increased, blurring this scheme and adding further phenotypes to the list. A broader disease spectrum could lead to misdiagnosis of different congenital myopathies, neurogenic atrophy and other neuromuscular conditions. Results As a result of a multicenter Italian study we collected clinical, histopathological and imaging data from a population of 21 cases from 15 families, carrying reported or novel mutations in MYH7. Patients displayed a variable phenotype including atypical pictures, as dropped head and bent spine, which cannot be classified in previously described groups. Half of the patients showed congenital or early infantile weakness with predominant distal weakness. Conversely, patients with later onset present prevalent proximal weakness. Seven patients were also affected by cardiomyopathy mostly in the form of non-compacted left ventricle. Muscle biopsy was consistent with minicores myopathy in numerous cases. Muscle MRI was meaningful in delineating a shared pattern of selective involvement of tibialis anterior muscles, with relative sparing of quadriceps. Conclusion This work adds to the genotype-phenotype correlation of MYH7-relatedmyopathies confirming the complexity of the disorder.
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.
