DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for myofibrillar myopathy 2 — 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 moduleMyofibrillar myopathy 2 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 myofibrillar myopathy 2 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
crystallin alpha B (CRYAB) — CRYAB 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 2YGD · 9.4 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 2008 imaging study of 46 patients with myofibrillar myopathy, distinct muscle involvement patterns helped separate genetic subtypes. For desminopathy, the semitendinosus was at least as affected as the biceps femoris, and the peroneal muscles were never less involved than the tibialis anterior; these criteria had 100% sensitivity and 95% specificity for detecting desminopathy in that cohort. For myotilinopathy, the adductor magnus showed more alterations than the gracilis, and the sartorius was at least as affected as the semitendinosus (sensitivity 90%, specificity 93%). For filaminopathy, the biceps femoris and semitendinosus were at least as affected as the sartorius, and the medial gastrocnemius was more affected than the lateral gastrocnemius (sensitivity 88%, specificity 96%). Early adult onset and cardiac involvement were most often associated with desminopathy; filaminopathy typically began in the fifth decade with proximal weakness, while myotilinopathy presented after age 50 with distal weakness.
A 2004 study of eight patients from four families examined protein kinase C isoforms and interleukin-1β in myofibrillar myopathy muscle. Immunohistochemistry showed expression of alpha, eta, and zeta isoforms of protein kinase C, as well as interleukin-1β, in abnormal muscle fibres. Immunoblots confirmed these findings and showed that protein kinase C delta and epsilon were absent in both patients and controls. The authors suggested that protein kinase C and interleukin-1β may play a role in the pathogenesis of the disease, but no therapeutic intervention was tested.
A 2021 review described myofibrillar myopathy as a pathologically defined group of disorders sharing myofibril dissolution, accumulation of degradation products, and ectopic protein expression. Patients present with progressive proximal or distal weakness at variable ages from childhood to late adulthood. Cardiomyopathy and peripheral neuropathy are common extramuscular features. Mutations in more than ten genes have been identified, most encoding Z disc–associated proteins or proteins involved in chaperone-assisted selective autophagy. No treatment trials were reported.
What is still missing is any clinical trial testing a drug in myofibrillar myopathy, whether repurposed or novel. The imaging and protein-expression studies provide diagnostic and mechanistic clues but no therapeutic data. Funding for a properly stratified trial, with genetic subtyping and outcome measures sensitive to slow progression, remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2008 · 261 citations · open access
Distinct muscle imaging patterns in myofibrillar myopathies
AbstractOBJECTIVE: To compare muscle imaging findings in different subtypes of myofibrillar myopathies (MFM) in order to identify characteristic patterns of muscle alterations that may be helpful to separate these genetic heterogeneous muscular disorders. METHODS: Muscle imaging and clinical findings of 46 patients with MFM were evaluated (19 desminopathy, 12 myotilinopathy, 11 filaminopathy, 1 alphaB-crystallinopathy, and 3 ZASPopathy). The data were collected retrospectively in 43 patients and prospectively in 3 patients. RESULTS: In patients with desminopathy, the semitendinosus was at least equally affected as the biceps femoris, and the peroneal muscles were never less involved than the tibialis anterior (sensitivity of these imaging criteria to detect desminopathy in our cohort 100%, specificity 95%). In most of the patients with myotilinopathy, the adductor magnus showed more alterations than the gracilis muscle, and the sartorius was at least equally affected as the semitendinosus (sensitivity 90%, specificity 93%). In filaminopathy, the biceps femoris and semitendinosus were at least equally affected as the sartorius muscle, and the medial gastrocnemius was more affected than the lateral gastrocnemius. The semimembranosus mostly showed more alterations than the adductor magnus (sensitivity 88%, specificity 96%). Early adult onset and cardiac involvement was most often associated with desminopathy. In patients with filaminopathy, muscle weakness typically beginning in the 5th decade of life was mostly pronounced proximally, while late adult onset (>50 years) with distal weakness was more often present in myotilinopathy. CONCLUSIONS: Muscle imaging in combination with clinical data may be helpful for separation of distinct myofibrillar myopathy subtypes and in scheduling of genetic analysis.
Expression of protein kinase C isoforms and interleukin-1β in myofibrillar myopathy
AbstractBACKGROUND: The term myofibrillar myopathy refers to a rare and clinically heterogeneous group of muscle disorders. The pathogenesis of this myopathy is not well understood. The morphologic hallmark is myofibrillar destruction with abnormal expression of numerous proteins, most consistently of desmin. METHODS: The authors investigated eight patients with myofibrillar myopathy belonging to four families. They studied the role of different protein kinase C isoforms and of interleukin-1beta, a cytokine that might activate protein kinase C and, in addition, mediate myofibrillar proteolysis. RESULTS: Immunohistochemical analysis showed the expression of alpha, eta, and zeta isoforms of protein kinase C and of interleukin-1beta in abnormal muscle fibers. Immunoblots confirmed the immunohistochemical data and revealed the absence of protein kinase C delta and epsilon in muscle fibers from patients and controls. CONCLUSIONS: These data suggest that protein kinase C and interleukin-1beta may play a role in the pathogenesis of myofibrillar 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
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.
