DeCure for Charcot-Marie-Tooth disease axonal type 2V
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease axonal type 2V — 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 2V 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 2v 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
N-acetyl-alpha-glucosaminidase (NAGLU) — NAGLU 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 xyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4XWH · 2.32 Å · ligand Xylitol (XYL). Experimental structure, not a prediction.
What the evidence adds up to
Two novel mutations in dynamin-2 (DNM2) were found to cause purely axonal CMT in two families without primary myopathy, after screening exons 13 through 16 of the pleckstrin homology domain in a large series of patients who had no mutations in more common genes. A 2023 retrospective study of 64 patients with suspected CMT used multiplex ligation probe amplification, next-generation sequencing, and whole-exome sequencing. 25 patients (39%) were diagnosed by multiplex ligation probe amplification. Among 50 patients who then underwent next-generation sequencing for targeted CMT gene panels, 18 (36%) had pathogenic or likely pathogenic variants. Whole-exome sequencing on five patients with normal next-generation sequencing results gave an 80% diagnostic yield, higher in the childhood group. The same study noted that patients without a molecular diagnosis remain common, suggesting undiscovered genes or mechanisms.
A 2014 review states that CMT affects roughly one in 2500 people worldwide and remains untreatable; rehabilitation and surgical correction of skeletal deformities are the only available approaches. The review reports that recent randomised controlled trials with ascorbic acid failed. A 2015 article reviews physiotherapy techniques and sanatorium treatment recommendations based on personal observations. A 2019 report describes a second family with a dominantly inherited CMT harbouring the MFN2 mutation c.2222T>G (p.Leu741Trp), confirming its pathogenicity; disease onset in this family was much later than in previously reported cases. A 2024 clinical case review states that CMT remains a difficult problem for accurate diagnosis and effective treatment.
What is still missing are effective drug therapies validated in clinical trials, reliable biomarkers for patient stratification, and funding to move beyond the failure of ascorbic acid trials and the current reliance on physiotherapy and surgery. The genetic heterogeneity of CMT means that even with improved molecular diagnosis, many patients have no known mutation, and no trial has yet shown a drug that slows or reverses the neuropathy.
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.
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.
An update on clinical trials in Charcot-Marie-Tooth Disease
AbstractHow far away is an effective therapy for Charcot-Marie-Tooth disease (CMT), the most frequent inherited neuropathy affecting approximately one individual in every 2500 around the world [1]? The next few years will be fundamental to giving the answer to this key question about a still untreatable disorder, for which rehabilitation therapy and surgical correction of skeletal deformities still represent the only available approaches. Different lines of research are rapidly providing encouraging data on possible effective treatments in cellular and animal models, and clinical studies are progressively filling the gaps to be fully ready for clinical trials, creating great hope in patients and researchers alike. However, CMT poses a series of difficulties in the pathway to the cure and in running clinical trials, as testified to by the failure of recent randomized-controlled trials (RCT) with ascorbic acid.
DOAJ (DOAJ: Directory of Open Access Journals) · 2015 · 2 citations · open access
Physiotherapy of Charcot–Marie–Tooth disease
AbstractIn the article there is a review the latest achievements in the field of physiotherapy Charcot–Marie–Tooth disease (CMT). Describes some of the techniques non-pharmacological treatment, the goal of physiotherapy application depending on the pathogenesis, clinical manifestations of the disease, electromiographic tests. Here there are recommendations for sanato¬rium treatment. On the basis of personal observations in the article presents the author's patterns of treatment for CMT patients.
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.
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.
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.
