DeCure for Charcot-Marie-Tooth disease X-linked recessive 5
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease X-linked recessive 5 — 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 5 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 5 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
phosphoribosyl pyrophosphate synthetase 1 (PRPS1) — PRPS1 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 hsxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8DBE · 2.1 Å · ligand 5-O-phosphono-alpha-D-ribofuranose (HSX). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 report describes a family with Charcot-Marie-Tooth disease showing an irregular dominant sex-linked inheritance pattern. No linkage was found between the Xg(a) blood group locus and the CMT locus. Abnormal serum alkaline phosphatase levels were observed in both affected and unaffected family members, making the relevance of that finding unclear.
A 2023 retrospective study analysed 64 patients (33 male, 31 female) with suspected CMT using three molecular methods. Multiplex ligation probe amplification diagnosed 25 patients (39%). 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 was performed on five patients with normal next-generation sequencing results, achieving an 80% diagnostic yield, which was higher in the childhood group. The authors note that patients without a molecular diagnosis remain in all published series, suggesting undiscovered genes or mechanisms.
A 2019 review states that more than 90 causative genes for CMT have been identified. It notes that previous animal studies reported some molecules with therapeutic effects on specific CMT subtypes depending on the underlying genetic cause, and that induced pluripotent stem cell research has expanded possibilities for patient-specific cell therapy and drug discovery. However, no specific drugs or clinical trial results are given. A 2019 report of a second family with a dominantly inherited CMT and an MFN2 c.2222T>G (p.Leu741Trp) mutation confirms the mutation’s pathogenicity, but disease onset in this family was much later than in previously reported cases. A 1985 study of Gm and Km immunoglobulin allotypes in 46 Caucasian CMT patients found no significant association and no co-inheritance of Gm haplotypes with CMT.
What is still missing is a proven therapy for any CMT subtype, including X-linked recessive forms. The genetic heterogeneity means that even if a drug were tested, patient stratification by precise mutation would be required. No clinical trial data for any drug in CMT5 or X-linked CMT5 are provided in these abstracts. Funding for large, genetically stratified trials and for discovery of the missing causative genes remains the limiting factor.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Neurology · 2008 · 24 citations
Charcot-Marie-Tooth Disease with Sex-Linked Inheritance, Linkage Studies and Abnormal Serum Alkaline Phosphatase Levels
AbstractA family with Charcot-Marie-Tooth disease (CMT) is described. An irregular dominant sex-linked inheritance is observed. No linkage relationship between the Xg(a) blood group locus and the CMT locus was established. Abnormal values of the serum alkaline phosphatase level were found in affected and unaffected members.
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.
AbstractCharcot-Marie-Tooth disease (CMT) encompasses the heritable motor and sensory neuropathies that comprise most of the inherited peripheral neuropathies. Due to the great genetic heterogeneity of the condition, it can be difficult to determine what type of CMT a person has. The major phenotypic features of the CMT subtypes are delineated, as well as recommendations for focused genetic testing.
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 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.
International Journal of Immunogenetics · 1985 · 1 citations
G<scp>m</scp> AND K<scp>m</scp> ALLOTYPES IN CHARCOT‐MARIE‐TOOTH DISEASE
AbstractGm and Km immunoglobulin allotypes were studied in 46 Caucasian patients with Charcot-Marie-Tooth disease (CMT). No significant association of Gm and Km phenotypes with CMT was found. Family studies revealed that Gm haplotypes and CMT were not inherited together, thus arguing against the involvement of immunoglobulin allotypes in CMT.
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.
