DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease type 2 — screening already-approved drugs against its 20-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 type 2 maps to a 20-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 type 2 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
phosphoglycerate kinase 1 (PGK1) — PGK1 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9FDF · 1.44 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
In a retrospective study of 64 patients with suspected Charcot-Marie-Tooth disease, 25 (39%) were diagnosed by multiplex ligation probe amplification. Among 50 patients who then underwent next-generation sequencing for targeted gene panels, 18 (36%) had pathogenic or likely pathogenic variants. Whole-exome sequencing on five patients with normal next-generation sequencing results gave a diagnostic yield of 80%, higher in the childhood group. The authors note that patients without a molecular diagnosis persist across the literature, suggesting undiscovered genes or mechanisms.
Clinical trials registered on ClinicalTrials.gov for Charcot-Marie-Tooth disorders rose from 1 in 1999 to 286 by June 2022. Academic settings accounted for 91% of trials and pharmaceutical companies 9%. Only 38% of pharmaceutical trials and 28% of academic trials were controlled, randomised, and double-blinded. Of all trials, 86% were classified as therapeutic: 50% procedural (21% wrist or elbow surgery; 22% shock wave and hydrodissection therapy), 23% investigational drugs, 15% devices, and 11% physical therapy. Among therapeutic trials, 49% were phases 1–2 and 51% phases 3–4. Phase I human pharmaceutical trials are testing safety of small molecule therapies (n=8) and AAV and non-viral gene therapy (n=3). Preclinical animal gene therapy studies cover 11 different CMT forms using viral, CRISPR-Cas9, and nanoparticle delivery. Most molecular therapies remain in animal investigations.
Two reports confirm the pathogenicity of the MFN2 mutation c.2222T>G (p.Leu741Trp) in dominantly inherited CMT. A second family carrying this mutation showed a much later disease onset than previously reported cases. A separate clinical case describes phenotypic heterogeneity in 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 with the specific substitution.
What is still missing are adequately powered, randomised, double-blinded trials for the majority of investigational drug and gene therapy approaches. Most therapeutic trials are procedural rather than molecular. The diagnostic gap—patients without a molecular diagnosis—indicates that current gene panels and sequencing methods do not capture all causative variants. Patient stratification by specific MFN2 mutation and age of onset is needed, as phenotypic heterogeneity is substantial. Funding for late-phase trials and for discovery of novel genes remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Frontiers in Neurology · 2023 · 5 citations · open access
Clinical trials in Charcot-Marie-Tooth disorders: a retrospective and preclinical assessment
AbstractObjective This study aimed to evaluate the progression of clinical and preclinical trials in Charcot-Marie-Tooth (CMT) disorders. Background CMT has historically been managed symptomatically and with genetic counseling. The evolution of molecular and pathologic understanding holds a therapeutic promise in gene-targeted therapies. Methods ClinicalTrials.gov from December 1999 to June 2022 was data extracted for CMT with preclinical animal gene therapy trials also reviewed by PubMed search. Results The number of active trials was 1 in 1999 and 286 in 2022. Academic settings accounted for 91% and pharmaceutical companies 9%. Of the pharmaceutical and academic trials, 38% and 28%, respectively, were controlled, randomized, and double-blinded. Thirty-two countries participated: the United States accounted for 26% (75/286). In total, 86% of the trials were classified as therapeutic: 50% procedural (21% wrist/elbow surgery; 22% shock wave and hydrodissection therapy), 23% investigational drugs, 15% devices, and 11% physical therapy. Sixty-seven therapeutic trials (49%) were designated phases 1–2 and 51% phases 3–4. The remaining 14% represent non-therapeutic trials: diagnostic testing (3%), functional outcomes (4%), natural history (4%), and standard of care (3%). One-hundred and three (36%) resulted in publications. Phase I human pharmaceutical trials are focusing on the safety of small molecule therapies ( n = 8) and AAV and non-viral gene therapy ( n = 3). Preclinical animal gene therapy studies include 11 different CMT forms including viral, CRISPR-Cas9, and nanoparticle delivery. Conclusion Current CMT trials are exploring procedural and molecular therapeutic options with substantial participation of the pharmaceutical industry worldwide. Emerging drug therapies directed at molecular pathogenesis are being advanced in human clinical trials; however, the majority remain within animal investigations.
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.
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.
