DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease type 3 — screening already-approved drugs against its 5-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 3 maps to a 5-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 3 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
myelin protein zero (MPZ) — MPZ 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8IIA · 2.09 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2023 review of clinical trials in Charcot-Marie-Tooth disorders found that the number of active trials rose from 1 in 1999 to 286 in 2022. Academic settings accounted for 91% of trials and pharmaceutical companies for 9%. Of the pharmaceutical and academic trials, 38% and 28% respectively were controlled, randomised, and double-blinded. 86% of all trials were classified as therapeutic: 50% were procedural (21% wrist or elbow surgery, 22% shock wave and hydrodissection therapy), 23% were investigational drugs, 15% devices, and 11% physical therapy. 67 therapeutic trials (49%) were designated phases 1–2 and 51% phases 3–4. 103 trials (36%) resulted in publications. Phase I human pharmaceutical trials are focusing on 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 including viral, CRISPR-Cas9, and nanoparticle delivery.
A 2020 nationwide population-based study in Korea identified 2,885 CMT patients from 2005 to 2018. The prevalence per 100,000 persons in 2018 was 5.2 (6.1 for men, 4.4 for women), peaking at ages 15–39 years with almost twice as many men (n=714) as women (n=402) in that age group. 226 patients (7.8%) were receiving medical aid at diagnosis and 253 (8.8%) at last follow-up or death. From 2005 to 2017, 170 patients died (118 men, 52 women). The standardised mortality ratio was 1.57 (95% CI 1.34–1.83) for all patients and did not differ between sexes. Age-specific SMR was highest in patients 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.
A 2019 report described a second family with a dominantly inherited CMT harbouring the c.2222T>G (p.Leu741Trp) mutation in MFN2, confirming the pathogenicity of this mutation. The disease onset in this second family was much later than in previously reported cases.
No abstract in this set reports results from a completed randomised controlled trial of a drug for CMT type 3 specifically. What is missing is any phase 3 efficacy data for a molecular therapy in any CMT subtype, adequate patient stratification by genetic form in trials, and funding for late-stage trials that are not procedural or device-based.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
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.
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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