DeCure for Charcot-Marie-Tooth disease axonal type 2K
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease axonal type 2K — 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 2K 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 2k 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 novel dynamin-2 (DNM2) mutations were found in two families with purely axonal Charcot-Marie-Tooth disease (CMT) after screening exons 13 through 16 of the DNM2 gene in a large series of patients who had no mutations in more common genes and a broad range of nerve conduction velocities. The mutations cosegregated with the neuropathy, and no clinical evidence of primary myopathy was reported. The authors concluded that patients with axonal CMT type 2 without mutations in common genes should be investigated for DNM2 pleckstrin homology domain mutations. No sample size, survival, or response rates are given because this is a genetic discovery study, not a trial.
A 2024 case report describes a patient with a novel MORC2 variant who presented with an intermediate phenotype between CMT type 2Z and DIGFAN (developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy). The authors note that the genotype-phenotype correlation in MORC2-related disorders is complex and that the same mutation can cause a variety of phenotypes. This is a single case, so no generalisable numbers are available.
A 2025 report on CMT type 2A, the most common axonal form, caused by mutations in the MFN2 gene, describes a single patient with the c.1091G>C (p.Arg364Pro) missense mutation. The authors state that more than 100 missense mutations in MFN2 have been registered and that clinical presentation varies depending on the specific substitution. No treatment, survival, or response data are provided.
What is still missing: large, well-phenotyped cohorts to establish reliable genotype-phenotype correlations for DNM2, MORC2, and MFN2 mutations; functional studies to clarify how specific mutations cause axonal degeneration; and any clinical trial testing a drug that modifies disease course in these genetic subtypes. No drug is mentioned 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.
Neurology · 2007 · 88 citations
Two novel mutations in dynamin-2 cause axonal Charcot–Marie–Tooth disease
AbstractBACKGROUND: Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot-Marie-Tooth disease (CMT) type B. OBJECTIVE: To assess the etiologic role of DNM2 in CMT. METHODS: We performed a mutational screening of DNM2 exons 13 through 16 encoding the pleckstrin homology domain in a large series of CMT patients with a broad range of nerve conduction velocities and without mutations in more common genes. RESULTS: We identified two novel DNM2 mutations that cosegregated with purely axonal CMT in two pedigrees without clinical evidence of primary myopathy. CONCLUSION: Patients with axonal Charcot-Marie-Tooth disease type 2 neuropathy without mutations in more common genes should undergo investigation for DNM2 pleckstrin homology.
Human Genome Variation · 2024 · 2 citations · open access
Intermediate phenotype between CMT2Z and DIGFAN associated with a novel MORC2 variant: a case report
AbstractCharcot-Marie-Tooth disease type 2Z is caused by MORC2 mutations and presents with axonal neuropathy. MORC2 mutations can also manifest as developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN). We report a patient exhibiting an intermediate phenotype between these diseases associated with a novel MORC2 variant. A literature review revealed that the genotype‒phenotype correlation in MORC2-related disorders is complex and that the same mutation can cause a variety of phenotypes.
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.
Therapeutic Challenges in the Use of Chemotherapy and Cyclin-Dependent Kinase 4/6 Inhibitors in a Patient With Charcot-Marie-Tooth Disease and Breast Cancer
AbstractWe report a rare clinical scenario involving a 65-year-old female patient with Charcot-Marie-Tooth (CMT) disease who was diagnosed with early-stage breast carcinoma. The patient underwent neoadjuvant chemotherapy, followed by surgery and adjuvant endocrine therapy. During treatment, she developed grade 3 peripheral neuropathy, leading to the early discontinuation of paclitaxel and subsequent therapeutic adjustments. This report highlights the challenges of managing patients with neuromuscular comorbidities undergoing chemotherapy and the use of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors as adjuvant therapy in breast cancer treatment.
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.
