DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for myopathy, congenital, with tremor — 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 moduleMyopathy, congenital, with tremor 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 myopathy, congenital, with tremor 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 binding protein C1 (MYBPC1) — MYBPC1 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 2YXM · 1.51 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2021 review describes myogenic tremor as a novel entity first reported in 2019, believed to originate in the muscle itself rather than the central nervous system. It manifests as a high-frequency, postural, and kinetic tremor with onset in infancy. To date, only myopathies affecting the contractile elements, specifically myosin and a myosin-associated protein, have been recognised to feature myogenic tremor. The review states that the presence of myogenic tremor strongly points toward a sarcomere-associated mutation and may be a valuable clinical tool for differential diagnosis of myopathies.
A 2023 case report provides electrophysiological characterisation of a tremor in an individual with a de-novo likely pathogenic variant in Myosin Heavy Chain 7 (MYH7). Electromyographic recordings from facial muscles and bilateral upper and lower extremities showed 10 to 11 Hz activity during muscle activation. There were intermittent episodes of significant left-right coherence that modulated across muscle groups, but no coherence between muscles at different levels of the neuraxis. The authors suggest the tremor may originate at the sarcomere level within muscles, but note that the stability of the tremor frequency suggests the presence of central oscillators at the segmental level.
A 2008 report describes a patient with distal myopathy with rimmed vacuoles (DMRV) who exhibited Parkinsonism with a severe writing tremor that responded poorly to levodopa. The patient had a D176V/V572L compound heterozygous mutation in the GNE gene. The authors raise the possibility that atypical Parkinsonism is a rare complication of DMRV associated with GNE mutation.
What is still missing is a clear understanding of the pathomechanism, specifically whether the tremor generator is entirely within the sarcomere or requires segmental central oscillators. No treatment trials have been conducted for myogenic tremor, and no drug is mentioned in any of these abstracts. Patient stratification by specific sarcomeric gene mutations has not been attempted in a therapeutic context.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2021 · 13 citations
Myogenic tremor – a novel tremor entity
AbstractPURPOSE OF REVIEW: Tremor is a common neurological symptom with a plethora of potential etiologies. Apart from physiological tremor, the vast majority of tremor syndromes are linked to a pacemaker in the central nervous system (CNS) or, less common, in the peripheral nervous system. Myogenic tremor is a novel tremor entity, first reported in 2019 and believed to originate in the muscle itself. In this review, we describe the clinical properties of myogenic tremor and discuss its presumed pathogenesis on the basis of all of the patient cases published so far. RECENT FINDINGS: Myogenic tremor manifests itself as a high frequency, postural, and kinetic tremor with onset in infancy. To date, only myopathies affecting the contractile elements, in particular myosin and a myosin-associated protein, have been recognized to feature myogenic tremor. The generator of the tremor is believed to be located in the sarcomere, with propagation and amplification of sarcomeric oscillatory activity through CNS reflex loops, similar to neuropathic tremor. SUMMARY: True myogenic tremor must be distinguished from centrally mediated tremor due to myopathies with central nervous system involvement, i.e., mitochondrial myopathies or myotonic dystrophies. The presence of myogenic tremor strongly points toward a sarcomere-associated mutation and may thus be a valuable clinical tool for the differential diagnosis of myopathies.
Movement Disorders Clinical Practice · 2023 · 3 citations · open access
Electrophysiological Characterization of a <scp><i>MYH7</i></scp> Variant with Tremor Phenotype
AbstractBackground: (Myosin-Binding Protein C) variants. Here we report for the first time an individual with tremor who was found to have a de-novo likely pathogenic variant in Myosin Heavy Chain 7 (MYH7 We provide a detailed electrophysiological characterization of the tremor syndrome in a human individual with a myopathy and this pathogenic MYH7 variant to provide further insight in the phenotypic spectrum and pathomechanism of myogenic tremors in skeletal sarcomeric myopathies. Methods: Electromyographic recordings were obtained from facial muscles, as well as bilateral upper and lower extremities. Results: 10 to 11 Hz activity was observed in the face and extremities during recordings with muscle activation. There were intermittent episodes of significant left-right coherence that would modulate across muscle groups throughout the recording, but no coherence between muscles at different levels of the neuraxis. Conclusions: A possible explanation for this phenomenon is that the tremor originates at the sarcomere level within muscles, which is then picked up by muscle spindles and leads to activating input to the neuraxis segment. At the same time, the stability of the tremor frequency does suggest the presence of central oscillators at the segmental level. Thus, further studies will be needed to determine the origin of myogenic tremor and to better understand the pathomechanism.
Atypical Parkinsonism in distal myopathy with rimmed vacuoles
AbstractA patient with distal myopathy with rimmed vacuoles (DMRV) exhibited Parkinsonism with a severe writing tremor that responded poorly to levodopa. Molecular genetic analysis revealed that the patient had the D176V/V572L compound heterozygous mutation in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Histopathological examination of a biopsied muscle specimen yielded findings compatible with those of DMRV, which is characterized by the presence of rimmed vacuoles without inflammatory cell infiltration in muscle fibers. The finding of normal cardiac meta-iodobenzylguanide uptake makes the possibility of incidental Parkinson's disease in this patient unlikely. These observations raise the possibility that atypical Parkinsonism is a rare complication of DMRV associated with GNE mutation.
Tremor and Other Hyperkinetic Movements · 2024 · 2 citations · open access
A Case of a Patient With MYH2-Associated Myopathy Presenting With a Chief Complaint of Hand Tremor
AbstractBackground: Postural tremor is an uncommon and often overlooked phenotype in skeletal myopathy, which may lead to diagnostic delays. Case report: A 21-year-old man presented with adolescent onset postural hand tremor as the initial symptom, followed by mild limb muscle weakness. Neurological examination showed restricted ocular motility without diplopia and myopathic facial appearance. A muscle biopsy showed a decrease in type 2A fibers. Whole-exome sequencing identified two novel compound heterozygous variants in MYH2 gene (NM_017534.6): c.505+2T>C and c.3565 del C. The diagnosis was further validated via bioinformatics analysis and confirmed through familial co-segregation by Sanger sequencing. Discussion: This report expands the mutational and phenotypic spectrum of MYH2-associated myopathy. We suggest that in the differential diagnosis of tremor, besides common neurogenic causes, myogenic etiology should also be considered. Highlights Hand tremor in this case expands the phenotype of MYH2-associated myopathy, enhancing our understanding of tremor origins. It underscores the importance of nuanced clinical assessment and genetic screening in complex tremor disorders.
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.
