DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for inborn mitochondrial myopathy — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleInborn mitochondrial myopathy maps to a 4-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 inborn mitochondrial myopathy 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
Two patients with progressive external ophthalmoplegia and mitochondrial myopathy were found to carry novel mutations in the mitochondrial MT-TN gene. A 52-year-old man had a heteroplasmic m.5669G>A mutation, and a 66-year-old woman had a novel m.5702delA mutation. In both cases, single-fibre analysis showed significantly higher mutation loads in cytochrome c oxidase-deficient fibres than in normal fibres, and a high threshold level for COX deficiency. The mutations were not detected in blood, urine sediment or buccal cells. The authors conclude that MT-TN is a hotspot for mutations causing sporadic progressive external ophthalmoplegia.
A retrospective study of 21 genetically confirmed paediatric mitochondrial myopathy cases in China reported that mitochondrial DNA point mutations were most common, found in 14 of 21 patients (66.7%). The most frequent point mutation was m.3243A>G, present in 9 of 15 patients (60%). Three patients (14.3%) had large-scale deletions, and four (19.0%) had pathogenic nuclear gene variants, including five variants in TK2 and two in SURF1. Over follow-up of up to 7 years, 10 patients (47.6%) developed cardiomyopathy, 13 (61.9%) had at least one episode of hypercapnic respiratory failure, 6 (28.6%) had recurrent respiratory failure requiring intubation, and 8 (38.1%) died. Three patients (14.3%) recovered from respiratory failure with nocturnal non-invasive BiPAP ventilation and achieved a relatively stable functional life. The study notes that progressive proximal myopathy was the most prevalent presentation and that respiratory failure is a critical risk factor for poor prognosis.
No drug treatment was tested or mentioned in either study. The paediatric study reports no pharmacological intervention; the only supportive therapy described is non-invasive ventilation. The genetic case reports describe diagnosis and characterisation only. There is no evidence from these abstracts that any drug alters the natural history of mitochondrial myopathy.
What is still missing is any controlled trial of a pharmacological agent for this disease, any data on drug repurposing, and any stratification of patients by genetic subtype that might inform a future trial. Funding for such trials, and a trial design that accounts for the genetic and clinical heterogeneity described here, remain 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.
Progressive external ophthalmoplegia associated with novel <i>MT</i> ‐ <i>TN</i> mutations
AbstractObjectives To describe two patients with progressive external ophthalmoplegia (PEO) and mitochondrial myopathy associated with mutations in mitochondrial DNA, encoding the tRNAAsn gene (MT-TN), which have not previously been published with clinical descriptions. Materials & Methods Two unrelated patients with PEO were clinically examined. Muscle biopsy was performed and investigated by exome sequencing, enzyme histochemistry, and immunohistochemistry. The level of heteroplasmy was investigated in single muscle fibers and in other tissues. Results Patient 1 was a 52-year-old man with ptosis, PEO, and exercise intolerance since childhood. Muscle biopsy demonstrated mitochondrial myopathy with frequent cytochrome c oxidase (COX)-deficient fibers and a heteroplasmic mutation, m.5669G>A in the MT-TN gene, resulting in a substitution of a highly conserved C to T in the T stem of tRNAAsn. Patient 2 was a 66-year-old woman with ptosis, PEO, and exercise intolerance since many years. Muscle biopsy demonstrated mitochondrial myopathy with frequent COX-deficient fibers. She had a novel m.5702delA mutation in MT-TN, resulting in loss of a highly conserved U in the anticodon stem of tRNAAsn. Single fiber analysis in both cases showed highly significant differences in mutation load between COX-deficient and COX-normal fibers and a high threshold level for COX deficiency. The mutations were not found in blood, urine sediment or buccal cells. Conclusion We describe two MT-TN mutations associated with PEO and mitochondrial myopathy, and their pathogenicity was demonstrated. Together with previous reports, the results indicate that MT-TN is a hot spot for mutations causing sporadic PEO.
INDIGO (University of Illinois at Chicago) · 2020 · 0 citations · open access
Table_2_Clinical Profile and Outcome of Pediatric Mitochondrial Myopathy in China.DOCX
Abstract<p>Introduction: Mitochondrial myopathy in children has notable clinical and genetic heterogeneity, but detailed data is lacking.</p><p>Patients and Methods: In this study, we retrospectively reviewed the clinical presentation, laboratory investigation, genetic and histopathological characteristics, and follow-ups of 21 pediatric mitochondrial myopathy cases from China.</p><p>Results: Twenty-four patients suspected with mitochondrial myopathy were enrolled initially and 21 were genetically identified. Fourteen patients were found to harbor mitochondrial DNA point mutations (14/21, 66.7%), including m.3243A>G (9/15, 60%), m.3303C>T (2/15, 13.3%), m.3302A>G (1/15, 6.7%), m.3250T>C (1/15, 6.7%), m.3251A>G (1/15, 6.7%), of whom 12 patients presented with progressive proximal mitochondrial myopathy (12/14, 85.7%). Three patients revealed large-scale deletion in blood or muscle tissue (3/21, 14.3%), presenting with Kearns-Sayer syndrome (1/3, 33.3%) or chronic progressive external ophthalmoplegia (2/3, 66.7%). Four patients were found to harbor pathogenic nuclear gene variants (4/21, 19.0%), including five variants in TK2 gene and two variants in SURF1 gene. During the follow-ups up to 7 years, 10 patients developed cardiomyopathy (10/21, 47.6%), 13 patients occurred at least once hypercapnic respiratory failure (13/21, 61.9%), six experienced recurrent respiratory failure and intubation (6/21, 28.6%), eight patients failed to survive (8/21, 38.1%). With nocturnal non-invasive ventilation of BiPAP, three patients recovered from respiratory failure, and led a relative stable and functional life (3/21, 14.3%).</p><p>Conclusion: Mitochondrial myopathy in children has great clinical, pathological, and genetical heterogeneity. Progressive proximal myopathy is most prevalent. Mitochondrial DNA point mutations are most common. And respiratory failure is a critical risk factor of poor prognosis.</p>
INDIGO (University of Illinois at Chicago) · 2020 · 0 citations · open access
Table_1_Clinical Profile and Outcome of Pediatric Mitochondrial Myopathy in China.DOCX
Abstract<p>Introduction: Mitochondrial myopathy in children has notable clinical and genetic heterogeneity, but detailed data is lacking.</p><p>Patients and Methods: In this study, we retrospectively reviewed the clinical presentation, laboratory investigation, genetic and histopathological characteristics, and follow-ups of 21 pediatric mitochondrial myopathy cases from China.</p><p>Results: Twenty-four patients suspected with mitochondrial myopathy were enrolled initially and 21 were genetically identified. Fourteen patients were found to harbor mitochondrial DNA point mutations (14/21, 66.7%), including m.3243A>G (9/15, 60%), m.3303C>T (2/15, 13.3%), m.3302A>G (1/15, 6.7%), m.3250T>C (1/15, 6.7%), m.3251A>G (1/15, 6.7%), of whom 12 patients presented with progressive proximal mitochondrial myopathy (12/14, 85.7%). Three patients revealed large-scale deletion in blood or muscle tissue (3/21, 14.3%), presenting with Kearns-Sayer syndrome (1/3, 33.3%) or chronic progressive external ophthalmoplegia (2/3, 66.7%). Four patients were found to harbor pathogenic nuclear gene variants (4/21, 19.0%), including five variants in TK2 gene and two variants in SURF1 gene. During the follow-ups up to 7 years, 10 patients developed cardiomyopathy (10/21, 47.6%), 13 patients occurred at least once hypercapnic respiratory failure (13/21, 61.9%), six experienced recurrent respiratory failure and intubation (6/21, 28.6%), eight patients failed to survive (8/21, 38.1%). With nocturnal non-invasive ventilation of BiPAP, three patients recovered from respiratory failure, and led a relative stable and functional life (3/21, 14.3%).</p><p>Conclusion: Mitochondrial myopathy in children has great clinical, pathological, and genetical heterogeneity. Progressive proximal myopathy is most prevalent. Mitochondrial DNA point mutations are most common. And respiratory failure is a critical risk factor of poor prognosis.</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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