DeCure for Charcot-Marie-Tooth disease axonal type 2O
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease axonal type 2O — 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 2O 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 2o 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
dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) — DYNC1H1 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 9BLZ · 2.2 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Two novel mutations in dynamin-2 (DNM2) were found in two families with purely axonal Charcot-Marie-Tooth disease (CMT) without clinical evidence of primary myopathy. The mutations were identified by screening exons 13 through 16 of the DNM2 gene, which encode the pleckstrin homology domain, in a large series of CMT patients who had a broad range of nerve conduction velocities and no mutations in more common genes. The authors concluded that patients with axonal CMT type 2 neuropathy without mutations in more common genes should be investigated for DNM2 pleckstrin homology domain mutations. No treatment or drug was studied.
A 2024 case report describes a patient with an intermediate phenotype between CMT type 2Z and DIGFAN (developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy) associated with a novel MORC2 variant. The report notes that the genotype-phenotype correlation in MORC2-related disorders is complex and that the same mutation can cause a variety of phenotypes. No treatment or drug was studied.
A 2025 report describes phenotypic heterogeneity in CMT type 2A associated with the c.1091G>C missense mutation (p.Arg364Pro) in the MFN2 gene. CMT2A is the most common axonal form of the disease, caused by mutations in mitofusin-2, with more than 100 missense mutations registered. The report presents a single clinical case showing the peculiarities of the phenotype for that specific substitution. No treatment or drug was studied.
Across these abstracts, no drug repurposing, no clinical trial, and no therapeutic intervention of any kind is reported. What is missing is any funded effort to test a drug in these genetically defined CMT subtypes, any trial design that accounts for the marked phenotypic heterogeneity described, and any patient stratification strategy that could make a trial interpretable.
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.
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.
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.
