DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease type 4K — 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 type 4K 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 type 4k 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.
What the evidence adds up to
Charcot-Marie-Tooth disease type 4J is a recessive neuropathy caused by mutations in the lipid phosphatase FIG4. In a 2011 study of 11 previously unreported patients, ten had the compound heterozygous genotype FIG4(I41T/null) and one had FIG4(L17P/null). The I41T allele frequency in 5769 Northern European controls was 0.001. Severity ranged from mild signs to wheelchair dependence, and both mild and severe forms occurred with the same genotype. Onset and severity were highly variable; patients showed proximal and distal asymmetric muscle weakness, denervation on electromyography in both proximal and distal muscles, and frequent progression to severe amyotrophy. The authors noted that FIG4 mutations should be considered in patients with sporadic or recessive inheritance, childhood onset, and a phase of rapid progression.
A 2020 nationwide Korean study of 2885 Charcot-Marie-Tooth patients from 2005 to 2018 reported a 2018 prevalence of 5.2 per 100,000 persons, peaking at ages 15–39 with nearly twice as many men as women in that age group. Of the patients, 7.8% were receiving medical aid at diagnosis and 8.8% at last follow-up or death. Over the study period, 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 sex difference. Age-specific mortality was highest in patients under 9 years. Neurologic disease as a cause of death was significantly more frequent in Charcot-Marie-Tooth patients than in the general population.
A 2019 study of a single family of six with Charcot-Marie-Tooth phenotypes examined the Reticulon 4 (RTN4) gene for a possible role in the disease. Sequencing found a missense mutation in exon 2 in the proband, but after checking pathogenicity the authors concluded that RTN4 was not involved in causing Charcot-Marie-Tooth disease type 1. No drug or treatment was tested or proposed in that study.
What remains missing for Charcot-Marie-Tooth disease type 4K specifically is any clinical trial of a drug, any preclinical testing of a repurposed compound, and any patient stratification beyond genotype. No abstract here reports a treatment outcome, a response rate, or a survival benefit for any drug. Funding for a natural history study or a trial in FIG4-mutant patients is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brain · 2011 · 124 citations · open access
Distinctive genetic and clinical features of CMT4J: a severe neuropathy caused by mutations in the PI(3,5)P2 phosphatase FIG4
AbstractCharcot-Marie-Tooth disease is a genetically heterogeneous group of motor and sensory neuropathies associated with mutations in more than 30 genes. Charcot-Marie-Tooth disease type 4J (OMIM 611228) is a recessive, potentially severe form of the disease caused by mutations of the lipid phosphatase FIG4. We provide a more complete view of the features of this disorder by describing 11 previously unreported patients with Charcot-Marie-Tooth disease type 4J. Three patients were identified from a small cohort selected for screening because of their early onset disease and progressive proximal as well as distal weakness. Eight patients were identified by large-scale exon sequencing of an unselected group of 4000 patients with Charcot-Marie-Tooth disease. In addition, 34 new FIG4 variants were detected. Ten of the new CMT4J cases have the compound heterozygous genotype FIG4(I41T/null) described in the original four families, while one has the novel genotype FIG4(L17P/nul)(l). The population frequency of the I41T allele was found to be 0.001 by genotyping 5769 Northern European controls. Thirty four new variants of FIG4 were identified. The severity of Charcot-Marie-Tooth disease type 4J ranges from mild clinical signs to severe disability requiring the use of a wheelchair. Both mild and severe forms have been seen in patients with the same genotype. The results demonstrate that Charcot-Marie-Tooth disease type 4J is characterized by highly variable onset and severity, proximal as well as distal and asymmetric muscle weakness, electromyography demonstrating denervation in proximal and distal muscles, and frequent progression to severe amyotrophy. FIG4 mutations should be considered in Charcot-Marie-Tooth patients with these characteristics, especially if found in combination with sporadic or recessive inheritance, childhood onset and a phase of rapid progression.
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.
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.
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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