DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for rhabdomyolysis-myalgia syndrome — 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 moduleRhabdomyolysis-myalgia syndrome 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 rhabdomyolysis-myalgia syndrome 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
ryanodine receptor 1 (RYR1) — RYR1 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 6UHS · 2.46 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Rhabdomyolysis is the acute breakdown of skeletal myofibres, most commonly triggered by toxins and overexertion. In a retrospective study of 51 patients presenting to a Turkish emergency department with creatine kinase levels above 5000 U/L (range 5052 to 59140 U/L, median 7882 U/L), the most common cause in the history was exercise (19.6%). Extremity pain was the most frequent presenting complaint (23.5%). Acute renal failure developed in 4 patients (8.8%), 21 patients (41.1%) were admitted to hospital wards, and 1 patient (1.9%) died. The authors note that rhabdomyolysis can be life-threatening and should be considered even when trauma is absent.
In six patients with severe, recurrent rhabdomyolysis beginning typically in the teenage years, bi-allelic loss-of-function variants in the OBSCN gene (encoding obscurin) were identified. Patient muscle showed reduced OBSCN expression and loss of obscurin protein. Cultured myoblasts from these patients were more susceptible to starvation, showing a greater decrease in sarcoplasmic reticulum calcium content compared to control myoblasts, which the authors interpret as lower efficiency of calcium pumping back into the sarcoplasmic reticulum or reduced calcium storage capacity when metabolism is impaired. None of the six patients had cardiomyopathy, and cardiac examinations were normal in all who were assessed; no first-degree relatives had a history of cardiomyopathy. The cohort is young, and the authors state that follow-up and additional cases are needed to delineate the clinical course of OBSCN-related disease.
A separate case series of four patients with acute rhabdomyolysis from different causes (carnitine palmitoyltransferase I deficiency presenting as compartment syndrome, acute polymyositis, Epstein-Barr virus-associated myositis, and glycyrrhizin- and diuretic-induced hypokalemic myopathy) showed that T2-weighted MRI revealed high-intensity lesions in affected muscles that correlated precisely with symptoms and neurological deficits. Repeat MRI demonstrated that these high-intensity lesions resolved in parallel with clinical improvement, suggesting they represent transient oedema rather than permanent myopathic changes.
What remains missing is a clear genetic diagnosis for most patients with recurrent rhabdomyolysis, as the authors of the OBSCN study note that most cases still lack a genetic explanation. Larger cohorts, longer follow-up to determine whether OBSCN variant carriers eventually develop cardiomyopathy, and prospective studies that stratify patients by trigger, genetic background, and renal outcomes are needed. No drug treatment is discussed in any of these abstracts.
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 Computer Assisted Tomography · 1993 · 51 citations
Repeat MRI in Acute Rhabdomyolysis
AbstractOBJECTIVE: Four cases of acute rhabdomyolysis are presented and the correlation between clinicopathological and MR findings is discussed. MATERIALS AND METHODS: The cases include carnitine palmitoyltransferase I deficiency presenting as compartment syndrome, acute polymyositis, acute myositis associated with Epstein-Barr virus infection, and glycyrrhizin- and diuretic-induced hypokalemic myopathy. RESULTS: The T2-weighted MR images revealed high intensity lesions in the affected muscle groups. The lesions seen on MR correlated precisely with the symptoms and neurological deficits of the patients. Repeat MR studies showed that the high intensity lesions seen on T2-weighted MR images resolved in parallel with the clinical course. CONCLUSION: This reversibility of the MR findings suggests that the high intensity lesions do not reflect permanent myopathic changes, but probably represent transient edema in the acute phase of rhabdomyolysis.
Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis
AbstractRhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified 10 bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in sarcoplasmic reticulum function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in sarcoplasmic reticulum Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the sarcoplasmic reticulum and/or a decrease in Ca2+ sarcoplasmic reticulum storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease.
Multiple cardiac arrests following an overdose of caffeine complicated by penetrating trauma
AbstractA 28-year-old man was admitted following a massive caffeine overdose and a self inflicted gunshot wound in an apparent suicide attempt. Although initially stable on admission, he subsequently suffered multiple cardiac arrests and generalised seizures within 23 h of admission; over the next 48 h, he developed rhabdomyolysis. The importance of early management in caffeine overdose is highlighted.
Northern Clinics of Istanbul · 2017 · 8 citations · open access
Evaluation of rhabdomyolysis cases that apply emergency service
AbstractOBJECTIVE: Rhabdomyolysis is a clinical and biochemical syndrome caused by skeletal muscle injury. Our aim was to contribute to the existing data on rhabdomyolysis in our country by evaluating the etiologic, demographic, and clinical features of rhabdomyolysis patients who applied to a tertiary hospital emergency department. METHODS: We retrospectively evaluated the data of patients who applied to the tertiary hospital emergency department from January 2015 to January 2016. The study population comprised patients admitted to the emergency department of our hospital with creatinine kinase levels above 5000 U/L at admission. The data of all cases that were included in the study were scanned by the researchers using the hospital's computer-based data recording system. Age, sex, creatine kinase levels, complaints, etiology, whether or not acute renal failure developed, hospitalization and discharge status, and clinic of hospitalization were screened for all patients. RESULTS: The creatine kinase levels of the patients at admission ranged from 5052 to 59140 U/L [median 7882 U/L (IQR: 7840)]. The most frequent (23.5%) cause of admission was extremity pain. The most common reason (19.6%) in the etiology was exercise. Twenty-one patients (41.1%) were admitted to clinics, and 1 patient (1.9%) died. Acute renal failure was observed in 4 patients (8.8%). CONCLUSION: Rhabdomyolysis is a clinical syndrome that can be life-threatening owing to muscle destruction. Although it is suspected after a traumatic injury, it should also be considered when other potential symptoms are observed. All clinicians should be aware of its common causes, diagnosis, and treatment options.
Steven Best is Assistant Professor of Philosophy at the University of Texas, El Paso. He has published widely on philosophy, cultural criticism, mass media, social theory, and postmodern theory. His books, all published by Guilford Press, New York, include Postmodern Theory: Critical Interrogations (with D. Kellner); The Politics of Historical Vision: Marx, Foucault, and Habermas; The Postmodern Turn: Paradigm
AbstractRhabdomyolysis is a syndrome of muscle necrosis with subsequent release of intracellular content into the blood. There are various causes for rhabdomyolysis that include trauma, medications and rarely autoimmune conditions such as autoimmune myositis. Antisynthetase syndrome is an autoimmune condition characterized by positive antisynthetase antibody, myopathy, lung disease and arthritis. To our knowledge, rhabdomyolysis in antisynthetase syndrome has not been reported in the literature. In this report, we present a patient who presented with features of rhabdomyolysis and was diagnosed with antisynthetase syndrome. This patient was treated with systemic steroids with partial improvement, followed by rituximab, which led to significant improvement in his condition. In addition, we summarize all cases reported in the literature of inflammatory myopathy-associated rhabdomyolysis.
Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis
Abstract<p>Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified ten bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in SR function and Ca<sup>2+</sup> handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in SR Ca<sup>2+</sup> content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca<sup>2+</sup> back into the SR and/or a decrease in Ca<sup>2+</sup> SR storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease.</p>
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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