DeCure for Charcot-Marie-Tooth disease axonal type 2S
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease axonal type 2S — 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 axonal type 2S 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 axonal type 2s 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
immunoglobulin mu DNA binding protein 2 (IGHMBP2) — IGHMBP2 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 4B3F · 2.5 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Charcot-Marie-Tooth disease axonal type 2S is not mentioned in any of the provided abstracts. The abstracts describe CMT2A caused by a mitofusin 2 (MFN2) mutation, with one German patient carrying a spontaneous R94Q mutation who showed rapid progression in early years that later slowed, and no central nervous system involvement (2007). A 2005 report describes a Polish family with mild early-onset axonal CMT in which nine known CMT2 loci and the MPZ locus were excluded, suggesting a novel form. No specific drug or treatment is tested or proposed in any of these papers.
A 2019 review states that more than 90 causative genes for CMT have been identified, and that animal studies have reported some molecules with therapeutic effects on specific subtypes depending on the genetic cause, but gives no concrete drug names, survival figures, or response rates. The 2023 study reports a diagnostic yield of 39% by multiplex ligation probe amplification and 36% by next-generation sequencing in a cohort of 64 patients, with whole-exome sequencing achieving 80% diagnostic yield in five patients. That paper also notes that many patients remain without a molecular diagnosis, implying undiscovered genes or mechanisms.
A 2024 Russian-language review states that CMT remains a difficult problem for accurate diagnosis and effective treatment, but provides no new data, drug names, or outcomes. No abstract reports a clinical trial, a repurposed drug, or any measurable improvement in disease course. What is missing is any clinical trial testing a drug in CMT2S, any patient stratification by the specific genetic subtype, and funding for such a trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Neurology · 2007 · 33 citations · open access
AbstractCharcot-Marie-Tooth disease (CMT) has been classified into two types: demyelinating forms (CMT1) and axonal forms (CMT2). Mutations in the CMT2A locus have been linked to the KIF1B and the mitofusin 2 (MFN2) genes. Here, we report a German patient with CMT2 with an underlying spontaneous mutation (c.281G-->A) in the MFN2 gene. Clinically, the patient presented with early-onset CMT that was not associated with additional central nervous system pathology. The disease course was rapidly progressive in the first years and slowed afterwards. We also suggest that single patients with early-onset axonal polyneuropathies should be screened for MFN2 mutations.
Precision and Future Medicine · 2019 · 24 citations · open access
Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes
AbstractCharcot-Marie-Tooth disease (CMT) is one of the most common inherited neuropathies and is both genetically and clinically heterogeneous, with variable inheritance modes. With regard to clinical and genetic aspects, CMT is divided into several subtypes, including CMT1, CMT2, CMT3, CMT4, CMT5, CMT6, X-linked CMT, and intermediate CMT. Up to date, more than 90 causative genes for CMT have been identified. Furthermore, previous animal studies reported some molecules to have therapeutic effects on specific CMT subtypes, depending on the underlying genetic cause. Therefore, accurate genetic diagnosis is of crucial importance when performing customized therapy. Finally, recent investigations on induced pluripotent stem cells expanded the possibility of both patient-specific cell therapy and drug discovery. The current review focuses on the latest classification updates for accurate CMT diagnosis.
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.
Академический журнал Западной Сибири · 2024 · 1 citations · open access
Клинический случай болезни Шарко-Мари-Тута
AbstractCharcot-Marie-Tooth disease (CMT) is a rare inherited disorder of the peripheral nervous system characterized by degeneration of the myelin sheath and axial cylinders of nerve fibers.Currently, despite significant progress in medicine, Charcot-Marie-Tooth disease continues to remain a difficult problem in terms of accurate diagnosis and effective treatment.The review provides basic information on the diagnosis, clinical picture of the disease and treatment methods.
Mild early onset axonal Charcot-Marie-Tooth disease not linked to other axonal Charcot-Marie-Tooth loci
AbstractAutosomal dominant axonal Charcot-Marie-Tooth disease type 2 (CMT2) is a heterogeneous group of disorders with seven chromosomal loci mapped in the uncomplicated forms of CMT2. The authors report clinical, electrophysiologic, and genetic analysis of a Polish CMT2 family. Nine known CMT2 gene loci and one MPZ gene locus have been excluded. The authors' findings suggest that this family represents a novel form of CMT2 disease.
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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