DeCure for Charcot-Marie-Tooth disease X-linked recessive 4
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease X-linked recessive 4 — 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 X-linked recessive 4 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 x-linked recessive 4 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
apoptosis inducing factor mitochondria associated 1 (AIFM1) — AIFM1 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 faddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5KVI · 1.995 Å · ligand FLAVIN-ADENINE DINUCLEOTIDE (FAD). Experimental structure, not a prediction.
What the evidence adds up to
The 2023 retrospective study of 64 patients (33 male, 31 female) with suspected Charcot-Marie-Tooth disease found that 25 patients (39%) were diagnosed by multiplex ligation probe amplification. Among 50 patients who underwent next-generation sequencing for targeted gene panels, 18 (36%) had pathogenic or likely pathogenic variants. Whole-exome sequencing performed on five patients with normal next-generation sequencing results achieved an 80% diagnostic yield, higher in the childhood group. The authors note that patients without a molecular diagnosis persist across the literature, suggesting undiscovered genes or mechanisms.
A 2019 review states that more than 90 causative genes for CMT have been identified, and that previous animal studies reported some molecules with therapeutic effects on specific subtypes depending on the underlying genetic cause. The review emphasises that accurate genetic diagnosis is crucial for any customised therapy, and that induced pluripotent stem cell research has expanded possibilities for patient-specific cell therapy and drug discovery, but provides no clinical trial data.
A separate 2019 study investigated the Reticulon 4 (RTN4) gene in a family of six with CMT phenotypes. Sequencing found a missense mutation on exon 2 of RTN4 in the proband, but after checking pathogenicity the study concluded that RTN4 was not involved in causing CMT type 1. No drug or therapeutic intervention was tested.
A 2022 case report describes a novel mutation in the MPZ gene causing early-onset but slow-progressive CMT in a Russian family. The report provides no treatment data.
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.
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.
Journal of the Pakistan Medical Association · 2019 · 0 citations · open access
In-silico and Molecular Analysis of RTN4 as novel therapeutic option for axonal regeneration
AbstractOBJECTIVES: To find interactions of the ligand with axonali nhibitors, and to check the optimum interactions of existing drugs as inhibitors for the protein that hinders the growth of injured neurons. METHODS: The study was conducted at Kongju National University, Korea from May 2016 to March 2017. It consisted of two parts. Molecular analysis and bioinformatics analysis. The study comprised a family of six with Charcot-Marie-Tooth phenotypes, recommended by a neurologist for molecular analysis on the clinical symptoms to find the mutations responsible for the disease. Blood samples were collected from each family member and total deoxyribonucleic acid was extracted and it was analysed for Reticulon 4 gene by sequencing the coding and intronic regions. However, a missense mutation was found on exon 2 of the gene in the proband and the whole family was subsequently analysed. Bioinformatics analysis and docking studies were carried out to investigate the potential behaviour of Reticulon 4 as therapeutic agent. Sequencing analysis was performed to find the pathoegenic variant responsible for Charcot-Marie-Tooth type 1. RESULTS: After checking pathogenicity of the mutation, Reticulon 4 gene was found to be not involved in Charcot- Marie-Tooth disease type 1. CONCLUSIONS: Reticulon 4 gene was not found to be involved in causing Charcot-Marie-Tooth disease type 1.
Sage Journals Data · 2022 · 0 citations · open access
Research Data for Novel mutation in the <i>MPZ</i> gene causes early-onset but slow-progressive Charcot–Marie–Tooth disease in a Russian family: a case report
AbstractResearch Data for Novel mutation in the <i>MPZ</i> gene causes early-onset but slow-progressive Charcot–Marie–Tooth disease in a Russian family: a case report by Anastasiya Aleksandrovna Kozina, Natalia Vladimirovna Baryshnikova, Anna Yurievna Ilinskaya, Anna Alexandrovna Kim, Nikolay Alekseevich Plotnikov, Nadezhda Andreevna Pogodina, Ekaterina Ivanovna Surkova, Peter Alekseevich Shatalov and Valery Vladimirovich Ilinsky in Journal of International Medical Research
Iranian journal of child neurology. · 2020 · 0 citations · open access
Investigation of mutations in exon 14 of SH3TC2 gene and exon 7 of NDRG1 gene in Iranian Charcot Marie Tooth type 4 patient
AbstractCMT4 is an autosomal recessive form of Charcot-Marie-tooth disease which has shown more severity and earlier age of onset compared to other types of it, furthermore; CMT4C andCMT4D are the more prevalent types in Mediterranean countries due to higher incidence of consanguineous marriages. The most important aim of this study is to illuminate the rate of p.R148X mutation in NDRG1 gene and p.R1109X in SH3TC2 gene which are responsible genes for CMT4D and CMT4C respectively in Iranian population, Furthermore; this study investigated the probable other nucleotide changes in exon 14 of SH3TC2 gene and exon 7 of NDRG1 gene. In order to study this disease, 24 CMT4 affected individuals that they referred to Iran Special Medical Center, were clinically and electrophysiologically evaluated and selected for this study. The patients’ DNA was extracted from blood samples and after PCR, the products were sequenced and analyzed by Finch TV software. None of the founder mutations we were searching for were seen in this study. Sequencing of SH3TC2 gene showed SNP rs1025476 (g.57975C>T) in 21 patients (87.5%) that 7 individuals were homozygous and 14 individuals were heterozygous for this variant. Despite of high rate of considered mutations in some specific populations it seems that these mutations are very rare in Iranian CMT4 affected individuals. To clarify the association of SNP rs1025476 with CMT4, further assesments are needed and it could be helpful in knowing the Iranian population genetic markers and their genetic features.
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.
