DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for myofibrillar myopathy 6 — 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 6 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 6 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
Myofibrillar myopathy is a pathologically defined group of inherited progressive muscle wasting diseases for which there are no available treatments. Mutations in more than ten genes underlie the condition, most encoding Z disc–associated proteins or proteins involved in chaperone-assisted selective autophagy. Patients present with progressive proximal or distal weakness beginning anywhere from childhood to late adulthood; cardiomyopathy and peripheral neuropathy are frequent extramuscular complications.
A 2008 imaging study of 46 patients (19 desminopathy, 12 myotilinopathy, 11 filaminopathy, 1 alphaB-crystallinopathy, 3 ZASPopathy) found that distinct patterns of muscle involvement on MRI could separate subtypes with high sensitivity and specificity. 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 (sensitivity 100%, specificity 95%). 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 more 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; myotilinopathy presented after age 50 with distal weakness.
A 1999 study using the TUNEL method on six MFM muscle biopsies found no evidence of apoptotic myonuclei, arguing against apoptosis as a primary mechanism. The authors suggested mitotic catastrophe as an alternative possibility. A 2021 review noted that the common histopathologic features are dissolution of myofibrils, accumulation of degradation products, and ectopic expression of multiple proteins. A 2023 thesis stated that animal models had identified promising new therapies, but no drug names, response rates, or survival data were provided in any of the abstracts.
What is still missing: any human clinical trial data for a therapeutic compound, a clear molecular target validated in patients, and patient stratification beyond the imaging-based subtype separation described in 2008. No drug has been tested in a controlled trial for myofibrillar myopathy.
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.
Abnormal distribution of desmin and vimentin in myofibers in adult onset myotubular myopathy
AbstractWe report, for the first time, muscle immunocytochemical studies in sporadic, adult onset myotubular myopathy (SAOMM), which show intramyofibrillar central, perinuclear desmin and vimentin. This pattern was absent in a normal control and in myofibers with increased internal nuclei associated with denervation and myotonic muscular dystrophy (MyD). These findings resemble those reported in 8- to 15-week-old human fetal myotubes and myofibers of infantile MM, implying a possible regression of intermediate filaments of adult myofibers to an early developmental phase in SAOMM.
Myofibrillar myopathy: No evidence of apoptosis by TUNEL
AbstractThe pathogenesis of myofibrillar myopathy (MFM) is not known. Muscle biopsy specimens demonstrate increased expression of cell cycle regulatory proteins as well as the ectopic expression of lamin B and nuclear matrix protein in the cytoplasm, suggesting the possibility of apoptosis. The authors investigated for apoptosis using the TUNEL method in six muscle biopsy specimens from patients with MFM. There was no evidence of apoptotic myonuclei in any of the MFM muscle biopsies. Further studies regarding the pathogenesis of MFM and the possible role of mitotic catastrophe are needed.
Monash University · 2023 · 0 citations · open access
Exploring therapeutic compounds to treat myofibrillar myopathies
AbstractMyofibrillar myopathies are an inherited progressive muscle wasting disease for which there are currently no available treatments. Through the use of animal models, this thesis identified promising new therapies and established model systems to further investigate this group of diseases.
Exploring therapeutic compounds to treat myofibrillar myopathies
AbstractMyofibrillar myopathies are an inherited progressive muscle wasting disease for which there are currently no available treatments. Through the use of animal models, this thesis identified promising new therapies and established model systems to further investigate this group of diseases.
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
German Medical Science (German Research Foundation) · 2012 · 0 citations · open access
Loss of VCP leads to a myopathic phenotype
AbstractMyofibrillar myopathies (MFM) are progressive diseases of the heart and skeletal muscle that often lead to physical disability and premature death. Although several disease genes for MFM are known, the molecular pathomechanisms that translate the gene mutation into the myopathic phenotype are completely[for full text, please go to the a.m. URL]
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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