DeCure for Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy
DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy — 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, myofibrillar, 12, infantile-onset, with cardiomyopathy 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, myofibrillar, 12, infantile-onset, with cardiomyopathy 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 light chain 2 (MYL2) — MYL2 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
A 2014 case report describes a young woman with myofibrillar myopathy and restrictive cardiomyopathy whose recurrent atrial fibrillation and atrial tachycardias were intolerant to drug therapy. She underwent repeated radiofrequency ablations, which successfully treated the arrhythmias and led to regression of heart failure, postponing the need for cardiac transplantation. This is a single case, not a controlled trial, and the intervention is ablation of arrhythmia, not a drug.
A 2022 case report and literature review focuses on BAG3-related myopathy, the rarest form of myofibrillar myopathy. The common heterozygous Pro209Leu mutation in BAG3 is usually associated with rapidly progressive cardiomyopathy in childhood. However, the authors describe a male patient with that mutation who presented at age 7 with proximal lower limb weakness, became wheelchair-dependent by age 17, but at age 19 still had no evidence of cardiomyopathy. This confirms a wide phenotypic spectrum, meaning cardiac involvement is not inevitable even with the same mutation.
A 2021 review of the myofibrillar myopathy proteome notes that mutations in more than 10 genes underlie these disorders, most encoding Z disc–associated proteins or proteins involved in chaperon-assisted selective autophagy. The review does not report any drug treatment or clinical trial results.
No drug treatment for the underlying myopathy or cardiomyopathy is reported in any of these abstracts. What is missing is any clinical trial of a pharmacological agent, any systematic patient stratification by genotype or cardiac phenotype, and the funding to conduct such trials.
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 Cardiovascular Electrophysiology · 2014 · 3 citations
Repeated Radiofrequency Ablation of Atrial Tachycardia in Restrictive Cardiomyopathy Secondary to Myofibrillar Myopathy
AbstractMyofibrillar myopathy is characterized by nonhyaline and hyaline lesions due to mutations in nuclear genes encoding for extra-myofibrillar or myofibrillar proteins. Cardiac involvement in myofibrillar myopathy may be phenotypically expressed as dilated, hypertrophic, or restrictive cardiomyopathy. Radiofrequency ablation of atrial fibrillation and flutter has so far not been reported in myofibrillar myopathy. We report the case of a young female with myofibrillar myopathy and deteriorating heart failure due to restrictive cardiomyopathy and recurrent atrial fibrillation and atrial tachycardias intolerant to pharmacotherapy. Cardiac arrhythmias were successfully treated with repeat radiofrequency ablations and resulted in regression of heart failure, thus postponing the necessity for cardiac transplantation.
Journal of Clinical Neuromuscular Disease · 2022 · 3 citations
Wide Spectrum of Cardiac Phenotype in Myofibrillar Myopathy Associated With a Bcl-2-Associated Athanogene 3 Mutation: A Case Report and Literature Review
AbstractABSTRACT: Myofibrillar myopathy is a clinically and genetically heterogeneous group of muscle disorders characterized by myofibrillar degeneration. Bcl-2-associated athanogene 3 (BAG3)-related myopathy is the rarest form of myofibrillar myopathy. Patients with BAG3-related myopathy present with early-onset and progressive muscle weakness, rigid spine, respiratory insufficiency, and cardiomyopathy. Notably, the heterozygous mutation (Pro209Leu) in BAG3 is commonly associated with rapidly progressive cardiomyopathy in childhood. We describe a male patient with the BAG3 (Pro209Leu) mutation. The patient presented at age 7 years with muscle weakness predominantly in the proximal lower limbs. Histologic findings revealed a mixture of severe neurogenic and myogenic changes. His motor symptoms progressed rapidly in the next decade, becoming wheelchair-dependent by age 17 years; however, at the age of 19 years, cardiomyopathy was not evident. This study reports a case of BAG3-related myopathy without cardiac involvement and further confirmed the wide phenotypic spectrum of BAG3-related myopathy.
Neurology Genetics · 2021 · 0 citations · open access
A Window Into the Myofibrillar Myopathy Proteome
AbstractMyofibrillar myopathy is a pathologically diagnosed myopathy encompassing a clinically and genetically heterogeneous group of myopathies that share common histopathologic features of dissolution of myofibrils, accumulation of myofibrillar degradation products, and ectopic expression of multiple proteins.1 Patients with myofibrillar myopathy present with progressive proximal or distal predominant weakness at a variable age at onset, ranging from childhood to late adulthood. Cardiomyopathy and peripheral neuropathy are frequent extramuscular manifestations. To date, mutations in more than 10 genes underlie myopathies with myofibrillar pathology, most of which encodes Z disc–associated proteins or proteins involving in chaperon-assisted selective autophagy.1
The Clinical and Genetic Spectrum of Myofibrillar (Desmin) Myopathy
AbstractFour recent articles highlight the clinical and genetic heterogeneity of myofibrillar myopathy (MFM). As Goldfarb and colleagues describe in their review, MFM can manifest at ages ranging from infancy to late adulthood. Weakness can affect predominantly the proximal or distal extremities, the axial muscles, or facial and pharyngeal muscles, or it can be generalized. Some patients develop spinal rigidity, others severe respiratory muscle involvement. In still others, the primary feature is a cardiomyopathy characterized by cardiac arrhythmias or heart failure. If smooth muscle is affected, intestinal pseudo-obstructions can develop.
Most familial cases demonstrate autosomal-dominant inheritance, although autosomal-recessive inheritance occurs, and …
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.
