DeCure for Charcot-Marie-Tooth disease axonal type 2C
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease axonal type 2C — screening already-approved drugs against its 2-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 2C maps to a 2-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 2c 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
transient receptor potential cation channel subfamily V member 4 (TRPV4) — TRPV4 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 2~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8T1E · 2.77 Å · ligand [(2~{R})-2-[(~{Z})-hexadec-9-enoyl]oxy-3-[oxidanyl-[2-(trimethyl-$l^{4}-azanyl)ethoxy]phosphoryl]oxy-propyl] (~{Z})-docos-13-enoate (9ZR). Experimental structure, not a prediction.
What the evidence adds up to
Two novel mutations in the dynamin-2 gene (DNM2) were found in two families with purely axonal Charcot-Marie-Tooth disease (CMT) and no clinical evidence of primary myopathy. The mutations were in the pleckstrin homology domain, encoded by exons 13 through 16. The authors recommend that patients with axonal CMT type 2 who have no mutations in more common genes should be tested for DNM2 pleckstrin homology domain mutations.
A 2024 case report describes a patient with a novel MORC2 mutation who presented with an intermediate phenotype between CMT type 2Z and DIGFAN (developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy). The literature review in that report states that the genotype-phenotype correlation in MORC2-related disorders is complex and that the same mutation can cause a variety of phenotypes. A separate 2022 Japanese case of CMT2Z with a c.754C>T (p.R252W) substitution in MORC2 complicated by severe retinitis pigmentosa is also reported. That study found that MORC2 mutants were involved in a decrease in cell survival through induction of apoptosis, and the authors suggest the mutation might be involved in photoreceptor degeneration.
A 2024 Russian-language review states that CMT remains a difficult problem in terms of accurate diagnosis and effective treatment, despite significant progress in medicine. The review provides basic information on diagnosis, clinical picture, and treatment methods but does not report any new trial results or specific therapies.
What is still missing: no drug has been tested in a controlled trial for any of these genetic subtypes. There are no data on patient stratification by specific DNM2 or MORC2 mutation, and no funding is reported for a repurposing screen or preclinical model work in these genotypes.
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.
Neurology and Clinical Neuroscience · 2022 · 0 citations
Japanese case of <scp>Charcot–Marie–Tooth</scp> disease type <scp>2Z</scp> with severe retinitis pigmentosa
AbstractAbstract Charcot–Marie–Tooth disease type 2Z (CMT2Z) shows highly variable clinical features. We report the first Japanese CMT2Z patient with a c.754C>T (p.R252W) substitution of the MORC2 gene, complicating severe retinitis pigmentosa. The MORC2 mutants were involved in a decrease in cell survival through induction of apoptosis. Thus, the MORC2 mutation might be involved in the degeneration of photoreceptors and the development of retinitis pigmentosa.
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.
