DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease — screening already-approved drugs against its 41-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 maps to a 41-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 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
histidine triad nucleotide binding protein 1 (HINT1) — HINT1 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 taudrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6J64 · 0.95 Å · ligand 2-AMINOETHANESULFONIC ACID (TAU). Experimental structure, not a prediction.
What the evidence adds up to
Charcot-Marie-Tooth disease is a group of inherited peripheral neuropathies with great genetic complexity. A 2007 review noted that rapid advances in molecular genetics had highlighted this complexity, but that the evolution from a simple clinical classification to a complex molecular one had not facilitated understanding of the disease, and that different mutations of the same gene produce a range of phenotypes. A 2011 review confirmed that the genetic heterogeneity makes it difficult to determine what type of CMT a person has. A 2008 study of one family with sex-linked inheritance found no linkage relationship between the Xg(a) blood group locus and the CMT locus, and reported abnormal serum alkaline phosphatase levels in both affected and unaffected members.
A 2023 retrospective study of 64 patients (33 males, 31 females) with suspected CMT used three molecular methods. 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 was performed on five patients with normal next-generation sequencing results, yielding a diagnostic rate of 80%, higher in the childhood group. The study concluded that the presence of patients without a molecular diagnosis in all the literature suggests new genes or mechanisms remain to be discovered. A 2022 case report described a novel mutation in the MPZ gene causing early-onset but slow-progressive CMT in a Russian family.
A nationwide population-based study in Korea from 2005 to 2018 identified 2,885 CMT patients. The prevalence in 2018 was 5.2 per 100,000 persons (6.1 for men, 4.4 for women), peaking at ages 15–39 years with nearly twice as many men as women in that age group. 7.8% of patients were receiving medical aid at diagnosis, rising to 8.8% at last follow-up or death. From 2005 to 2017, 170 patients died (118 men, 52 women). The standardized mortality ratio was 1.57 (95% CI 1.34–1.83) for all patients, with no difference between sexes. Age-specific mortality was highest in patients under 9 years. Neurologic disease as a cause of death was significantly more frequent in CMT patients than in the general population.
What is still missing is a clear molecular diagnosis for a substantial proportion of patients, as the 2023 study and the literature indicate unknown genes or mechanisms remain. No therapy is described in these abstracts. The Korean study provides epidemiological data but does not address treatment. The field lacks large-scale, prospective trials that stratify patients by specific genetic subtypes, and the funding needed to conduct such trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2007 · 26 citations
Hereditary neuropathies
AbstractPURPOSE OF REVIEW: The purpose of this review is to help neurologists understand new concepts in hereditary neuropathies, from the clinician's point of view, in the molecular era after the burst of information regarding peripheral nerve biology. RECENT FINDINGS: Recent studies have focused on understanding the pathomechanisms involved in hereditary neuropathies. In the past year identification of new genes has slowed down since scientists have concentrated more on the function of genes causing Charcot-Marie-Tooth disease and Schwann cell-axon interactions to reveal the molecular cell biology of the disease. Animal models for the most common subtypes of human Charcot-Marie-Tooth disease are now available. SUMMARY: Rapid advances in the molecular genetics and cell biology of hereditary neuropathies have highlighted the great genetic complexity of Charcot-Marie-Tooth disease. The evolution from a simple clinical classification to a complex molecular one has not facilitated our understanding of the disease. Moreover, the new molecular classification is not simple to use as different mutations of the same gene produce a range of phenotypes. The clinicians have to look for specific clinical and electrophysiological clues to direct the patient to appropriate genetic testing.
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.
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.
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.
Supplementary Material for: Prevalence, Mortality, and Cause of Death in Charcot-Marie-Tooth Disease in Korea: A Nationwide, Population-Based Study
Abstract<b><i>Background:</i></b> Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous disorders that primarily affect the peripheral nervous system. Epidemiological studies of CMT have not yet been performed in Korea. <b><i>Objectives:</i></b> This study was performed to estimate the prevalence of CMT in Korea and the socioeconomic status, mortality, and causes of death of Korean patients with CMT. <b><i>Methods:</i></b> Data on patients with CMT were obtained from the rare intractable disease registry and the National Health Insurance Service for the years 2005–2018. <b><i>Results:</i></b> During the study period, 2,885 CMT patients were enrolled. The prevalence per 100,000 persons in 2018 was 5.2 (6.1 for men and 4.4 for women), peaking at ages 15–39 years, with almost twice as many men (<i>n</i> = 714) as women (<i>n</i> = 402) in this age group. Of the CMT patients, 226 (7.8%) were receiving medical aid, a public assistance program targeting poor individuals, at the time of diagnosis and 253 (8.8%) at last follow-up or death. From 2005 to 2017, 170 patients died, including 118 men and 52 women. The standardized mortality ratio (SMR) was 1.57 (95% CI 1.34–1.83) for all patients and did not differ in men and women. Age-specific SMR was highest in patients aged under 9 years, gradually declining thereafter. Neurologic disease as a cause of death was significantly more frequent in CMT patients than in the general population. <b><i>Conclusions:</i></b> This was the first nationwide epidemiologic study of CMT patients in Korea. This study confirmed the characteristics associated with the prevalence of and mortality from CMT by age and is the first to report the socioeconomic status and causes of death of CMT patients.
Sage Journals Data · 2022 · 0 citations · open access
sj-pdf-2-imr-10.1177_03000605221139718 - Supplemental material 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
AbstractSupplemental material, sj-pdf-2-imr-10.1177_03000605221139718 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
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.
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