DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease type 2A2 — screening already-approved drugs against its 3-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 type 2A2 maps to a 3-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 type 2a2 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
mitofusin 2 (MFN2) — MFN2 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6JFK · 1.997 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
The 2007 review notes that the molecular classification of Charcot-Marie-Tooth disease has become complex, with different mutations in the same gene producing a range of phenotypes, and that this has not made the disease easier to understand. A 2023 retrospective study of 64 patients with suspected Charcot-Marie-Tooth disease used multiplex ligation probe amplification, next-generation sequencing, and whole-exome sequencing. Among 50 patients who underwent next-generation sequencing for targeted gene panels, 18 (36%) had pathogenic or likely pathogenic variants. Whole-exome sequencing on five patients with normal next-generation sequencing results gave a diagnostic yield of 80%, higher in the childhood group. The study concluded that patients without a molecular diagnosis are still common, suggesting undiscovered genes or mechanisms.
Two case reports describe specific MFN2 mutations in Charcot-Marie-Tooth disease type 2A (CMT2A). A 2019 report of a family with the c.2222T>G (p.Leu741Trp) mutation in MFN2 confirmed its pathogenicity and noted a much later disease onset than previously reported cases with the same mutation. A 2025 clinical case describes a patient with CMT2A associated with the c.1091G>C (p.Arg364Pro) missense mutation in MFN2, highlighting the variability of clinical presentation depending on the specific mutation location. More than 100 missense mutations in MFN2 have been registered.
No clinical trial data for any drug treatment in CMT2A are presented in these abstracts. The evidence is limited to genetic diagnosis and descriptions of phenotypic variability. What is still missing is any randomised controlled trial of a therapeutic agent, adequate funding for such trials, and a clear strategy for patient stratification given the genetic and clinical heterogeneity of the disease.
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 · 2007 · 26 citations
Hereditary neuropathies
AbstractPURPOSE OF REVIEW: The purpose of this review is to help neurologists understand new concepts in hereditary neuropathies, from the clinician's point of view, in the molecular era after the burst of information regarding peripheral nerve biology. RECENT FINDINGS: Recent studies have focused on understanding the pathomechanisms involved in hereditary neuropathies. In the past year identification of new genes has slowed down since scientists have concentrated more on the function of genes causing Charcot-Marie-Tooth disease and Schwann cell-axon interactions to reveal the molecular cell biology of the disease. Animal models for the most common subtypes of human Charcot-Marie-Tooth disease are now available. SUMMARY: Rapid advances in the molecular genetics and cell biology of hereditary neuropathies have highlighted the great genetic complexity of Charcot-Marie-Tooth disease. The evolution from a simple clinical classification to a complex molecular one has not facilitated our understanding of the disease. Moreover, the new molecular classification is not simple to use as different mutations of the same gene produce a range of phenotypes. The clinicians have to look for specific clinical and electrophysiological clues to direct the patient to appropriate genetic testing.
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.
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.
S S Korsakov Journal of Neurology and Psychiatry · 2025 · 0 citations
Phenotypic heterogeneity of Charcot–Marie–Tooth type 2A disease associated with the c.1091G>C missense mutation (p.Arg364Pro) in the MFN2 gene
AbstractCharcot–Marie–Tooth disease belongs to the group of genetically and phenotypically heterogeneous sensory-motor polyneuropathies. Charcot–Marie–Tooth disease type 2A (CMT2A) is the most common axonal form of the disease caused by mutations in the mitofusin-2 gene (MFN2). More than 100 missense mutations in this gene have been registered to date. Many studies have demonstrated the variability of clinical presentation depending on the specific localization of the substitution. The presented clinical case shows the peculiarities of the phenotype of a patient with CMT2A disease associated with the c.1091G>C (p.Arg364Pro) missense mutation in the MFN2 gene.
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.
