DeCure for Charcot-Marie-tooth disease, axonal, type 2DD
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-tooth disease, axonal, type 2DD — 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 2DD 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 2dd 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
ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) — ATP1A1 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 y01drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7E20 · 2.7 Å · ligand CHOLESTEROL HEMISUCCINATE (Y01). Experimental structure, not a prediction.
What the evidence adds up to
Charcot-Marie-Tooth disease is an inherited neuropathy with more than 90 causative genes identified. The condition is divided into subtypes including CMT1, CMT2, CMT3, CMT4, CMT5, CMT6, X-linked CMT, and intermediate CMT. Animal studies have reported molecules with therapeutic effects on specific subtypes depending on the underlying genetic cause, and induced pluripotent stem cell research has opened possibilities for patient-specific cell therapy and drug discovery. Accurate genetic diagnosis is described as crucial for any customised therapy.
A second family with a dominantly inherited CMT harbouring the c.2222T>G (p.Leu741Trp) mutation in MFN2 has been reported, confirming the pathogenicity of that mutation. The disease onset in this second family was much later than in previously reported cases. Another report describes a patient with CMT2A associated with the c.1091G>C (p.Arg364Pro) missense mutation in MFN2, noting that more than 100 missense mutations in this gene have been registered and that clinical presentation varies depending on the specific localisation of the substitution. No treatment data, response rates, or survival figures are provided in any of these abstracts.
Orthotic management of CMT is discussed in a 1994 review, with four case studies presented, each having a different clinical picture. The article states that muscle grades, gait patterns, and knowledge of the disease's natural history help practitioners provide successful orthotic management. No drug intervention is mentioned in that report.
What is still missing: no clinical trial data for any drug in CMT2A or CMT2DD specifically; no patient stratification strategy based on the dozens of known mutations; no funding for trials that would test any repurposed compound in a genetically defined cohort.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
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.
JPO Journal of Prosthetics and Orthotics · 1994 · 1 citations
Orthotic Management of Charcot-Marie-Tooth
AbstractCharcot-Marie-Tooth Disease (CMT) is a neurological condition not commonly seen by orthotists. This article will review recent literature on histology, physical symptoms and classifications. Specific physical manifestations are discussed and illustrated. Four case studies are presented with each having a different clinical picture. Muscle grades and gait patterns as well as a knowledge of this disease's natural history will help practitioners to better provide successful orthotic management.
Internal Medicine · 2023 · 1 citations · open access
An Elderly Woman with Complaints of Pain and Hearing Loss, Diagnosed with CMT1A with <i>PMP22</i> Duplication
AbstractCharcot-Marie-Tooth (CMT) disease is a heterogeneous hereditary motor and sensory neuropathy of the peripheral nervous system, with CMT1A in particular being the most common form. We encountered a 76-year-old woman with CMT1A who had a history of pain attacks and hearing loss from a young age, with motor symptoms manifesting late in life. Her pain and hearing loss may have been related to CMT. Our case also raises the possibility that neuropathic pain and hearing loss may precede the classic motor symptoms of CMT1A.
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.
