DeCure for Charcot-Marie-Tooth disease X-linked dominant 6
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease X-linked dominant 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 moduleCharcot-Marie-Tooth disease X-linked dominant 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 charcot-marie-tooth disease x-linked dominant 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.
Molecular view
pyruvate dehydrogenase kinase 3 (PDK3) — PDK3 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1Y8O · 2.48 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
A 2023 retrospective study of 64 patients (33 male, 31 female) with suspected Charcot-Marie-Tooth disease used multiplex ligation probe amplification, next-generation sequencing, and whole-exome sequencing to find a molecular diagnosis. Multiplex ligation probe amplification diagnosed 25 patients (39%). Among 50 patients who then had next-generation sequencing for targeted gene panels, 18 (36%) carried pathogenic or likely pathogenic variants. Whole-exome sequencing was performed on five patients with normal next-generation sequencing results and achieved an 80% diagnostic yield, higher in the childhood group. The authors note that patients without a molecular diagnosis appear in all published literature, suggesting undiscovered genes or mechanisms remain.
A 2008 report describes a family with Charcot-Marie-Tooth disease showing irregular autosomal dominant transmission, trophic ulcers, neural deafness, and raised serum alkaline phosphatase in some younger siblings of affected and unaffected individuals. A 2019 report confirms the pathogenicity of the MFN2 mutation c.2222T>G (p.Leu741Trp) in a second family with dominantly inherited CMT, noting that disease onset in this second family was much later than in the first reported family. A 1974 study of a kindred from Southwestern Louisiana with 66 heterozygotes for a dominant gene causing Charcot-Marie-Tooth disease with nerve hypertrophy describes five homozygous offspring from two marriages between heterozygotes, comparing their clinical features to those of classic heterozygotes and discussing nerve-conduction time for detecting asymptomatic heterozygotes. A 2022 case report from a Russian family describes a novel mutation in the MPZ gene causing early-onset but slow-progressive Charcot-Marie-Tooth disease.
No drug treatment is mentioned in any of these abstracts. What is missing is any clinical trial testing a therapy for CMTX6 specifically, any patient stratification by the MFN2 mutation subtype, and funding for trials that would move beyond genetic diagnosis toward intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Revista da Associação Médica Brasileira · 2023 · 6 citations · open access
High diagnostic yield with algorithmic molecular approach on hereditary neuropathies
AbstractOBJECTIVE: Charcot-Marie-Tooth disease covers a group of inherited peripheral neuropathies. The aim of this study was to investigate the effect of targeted next-generation sequencing panels on the molecular diagnosis of Charcot-Marie-Tooth disease and its subtypes in routine clinical practice, and also to show the limitations and importance of next-generation sequencing in the diagnosis of Charcot-Marie-Tooth diseases. METHODS: This is a retrospective study. Three different molecular methods (multiplex ligation probe amplification, next-generation sequencing, and whole-exome sequencing) were used to detect the mutations related to Charcot-Marie-Tooth disease. RESULTS: In total, 64 patients (33 males and 31 females) with suspected Charcot-Marie-Tooth disease were analyzed for molecular etiology. In all, 25 (39%) patients were diagnosed by multiplex ligation probe amplification. With an extra 11 patients with normal PMP22 multiplex ligation probe amplification results that were consulted to our laboratory for further genetic analysis, a total of 50 patients underwent next-generation sequencing for targeted gene panels associated with Charcot-Marie-Tooth disease. Notably, 18 (36%) patients had pathogenic/likely pathogenic variants. Whole-exome sequencing was performed on five patients with normal next-generation sequencing results; the diagnostic yield by whole-exome sequencing was 80% and it was higher in the childhood group. CONCLUSION: The molecular etiology in Charcot-Marie-Tooth disease patients can be determined according to pre-test evaluation, deciding the inheritance type with pedigree analysis, the clinical phenotype, and an algorithm for the genetic analysis. The presence of patients without a molecular diagnosis in all the literature suggests that there are new genes or mechanisms waiting to be discovered in the etiology of Charcot-Marie-Tooth disease.
Family with Charcot-Marie-Tooth Disease Showing Unusual Biochemical-Clinical and Genetic Features
AbstractA family with Charcot-Marie-Tooth disease is described. An irregular autosomal dominant transmission is observed. Some unusual clinical symptoms were present, such as trophic ulcers and neural deafness. In one generation of sibships with affected and unaffected individuals, some younger sibs had raised serum alkaline phosphatase activities. A connection between the neurology cal disorder and these abnormal values may be assumed.
Journal of Neuromuscular Diseases · 2019 · 2 citations
Late onset CMT2A in a Family with an MFN2 Variant: c.2222T>G (p.Leu741Trp)
AbstractMutations in MFN2 cause a range of Charcot-Marie-Tooth disease (CMT) phenotypes with different inheritance patterns and underlying pathogenic mechanisms. Recently, a family with a dominantly inherited CMT harboring c.2222T>G (p.Leu741Trp) mutation in MFN2 has been reported for the first time. Here, we report a second family also with a dominantly inherited CMT harboring the same mutation, thereby confirming the pathogenicity of this mutation. Interestingly, the disease onset of this second family is much later than the previously reported cases.
Acta geneticae medicae et gemellologiae · 1974 · 1 citations · open access
Homozygous Expression of a Dominant Gene Causing Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)
AbstractThis study involves the presentation of a kindred from Southwestern Louisiana showing 66 individuals who were heterozygous for a rare dominant gene for a type of Charcot-Marie-Tooth disease with hypertrophy of peripheral nerves. Two marriages between heterozygotes resulted in the occurrence of five homozygous offsprings. Clinical features of these previously undescribed homozygotes are compared to the clinical features of the classic type of heterozygote. The value of using nerve-conduction time to detect the asymptomatic heterozygote for Charcot-Marie-Tooth disease is discussed.
INDIGO (University of Illinois at Chicago) · 2022 · 0 citations · open access
sj-pdf-2-imr-10.1177_03000605221139718 - Supplemental material for Novel mutation in the <i>MPZ</i> gene causes early-onset but slow-progressive Charcot–Marie–Tooth disease in a Russian family: a case report
AbstractSupplemental material, sj-pdf-2-imr-10.1177_03000605221139718 for Novel mutation in the <i>MPZ</i> gene causes early-onset but slow-progressive Charcot–Marie–Tooth disease in a Russian family: a case report by Anastasiya Aleksandrovna Kozina, Natalia Vladimirovna Baryshnikova, Anna Yurievna Ilinskaya, Anna Alexandrovna Kim, Nikolay Alekseevich Plotnikov, Nadezhda Andreevna Pogodina, Ekaterina Ivanovna Surkova, Peter Alekseevich Shatalov and Valery Vladimirovich Ilinsky in Journal of International Medical Research
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.
