DeCure for Intermediate Charcot-Marie-Tooth disease
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for intermediate Charcot-Marie-Tooth disease — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIntermediate Charcot-Marie-Tooth disease maps to a 3-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 intermediate 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
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
In a second family carrying the dominantly inherited MFN2 mutation c.2222T>G (p.Leu741Trp), disease onset was much later than in the first reported family, confirming the pathogenicity of this variant in late-onset CMT2A. No treatment or outcome data are reported for this family; the abstract only describes the genetic confirmation and the later age of onset.
A multidimensional scale called the CMT Pediatric Scale (CMTPedS) was developed to measure disease severity in children with CMT. The scale covers eight domains: symptoms, foot/ankle involvement, lower limb sensation, hand dexterity/strength, balance, and motor function. Items were collapsed to 5-point Likert scales using z-scores based on age and gender norms. Inter-rater reliability from four international centres testing eight children with CMT was good to excellent (ICC2,4 0.78–0.99). A multicentre natural history study of children aged 3–17 years with all types of CMT was underway, with 90 children recruited at the time of publication. The authors planned to use the final CMTPedS as the primary outcome in clinical trials of podiatric, pharmacological and surgical interventions.
A 2011 review of therapeutic strategies for CMT notes that clinical trials of ascorbic acid and experimental trials of curcumin and antiprogesterone were in progress. The review also mentions development of robot technology and brain machine interfaces as potential new therapy avenues. It states that elucidation of molecular mechanisms using cell culture, iPS cells, animal models, agents to suppress PMP22 expression, and read-through of stop codon methods were expected. The review emphasises that surrogate markers, improved clinical trial design, a nationwide diagnostic system, and assessment of natural history through international collaboration were still needed.
A 2022 case report describes a novel mutation in the MPZ gene causing early-onset but slow-progressive CMT in a Russian family. No treatment or quantitative outcome data are provided in the abstract; it is a genetic case report only.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Journal of Foot and Ankle Research · 2011 · 1 citations · open access
Development, reliability and validity of the Charcot‐Marie‐Tooth disease Pediatric Scale (CMTPedS)
AbstractCharcot-Marie-Tooth disease (CMT) causes peripheral nerve demyelination, progressive foot weakness, cavus deformity, difficulty walking and sensory loss. There is a need for accurate, sensitive and disease-relevant measures of young children through to adolescents with CMT to enable accurate assessment of baseline performance, monitor disease severity longitudinally, and determine responses to existing and novel foot and ankle interventions. Our objective was to develop a multidimensional scale to measure disease severity of children with CMT, known as the CMT Pediatric Scale (CMTPedS). The CMTPedS has undergone a thorough development process: (1) definition of the construct; (2) generation of the item pool; (3) choice of scoring format; (4) peer-review (face validity); (5) pilot testing; (6) standardised training; (7) inter-rater reliability of four international centres assessing eight children with CMT; (8) multicenter implementation. Findings of the development process: (1) the CMTPedS is a composite scale with broad application to measure disease severity of childhood CMT with eight domains capturing symptoms, foot/ankle involvement, lower limb sensation, hand dexterity/strength, balance, motor function; (2) a large pool of items generated from the literature were reduced based on disease-specificity, functional/patient-relevance, reliability/validity, published norms, test duration and ease of interpretation; (3) items collapsed to 5-point Likert scales using z-scores based on age/gender norms; (4) quality, appropriateness and suitability of items peer-reviewed by 23 expert clinicians/researchers/patient representatives at the 168th European Neuromuscular Centre International Workshop; (5) pilot-tested on four children with CMT to check for administration problems, item instructions, order and duration; (6) clinicians from USA, UK, Italy and Australia trained through workshops, online manual and video resources; (7) all items exhibited good to excellent inter-rater reliability (ICC2,40.78-0.99) (8) a multicenter natural history study of children with all types of CMT aged 3-17 years is underway, with 90 children recruited to date. Application and psychometric validation of the CMTPedS continues. We plan to apply the final CMTPedS as the primary outcome in clinical trials of podiatric, pharmacological and surgical interventions.
Rinsho Shinkeigaku · 2011 · 0 citations · open access
Therapeutic strategies for Charcot-Marie-Tooth disease
AbstractRecently, causative gene discovery and genetic diagnosis system for Charcot-Marie-Tooth disease (CMT) have been rapidly developed. These genetic information and research progress, however, have not been informed to medical staff and CMT patients. CMT-Japan, which is an association of Japanese CMT patients, has been organized in 2008. Many of CMTJ members have not been diagnosed genetically. Most of medical staff and CMT patients may imagine that there is no hope for the CMT feature. Research on CMT therapy, however, has been progressing such as clinical trial of ascorbic acid, and experimental trial of curcumin and antiprogesterone. The development of robot technology and brain machine interface open a new way of therapy for CMT. Elucidation of molecular mechanisms and finding of effective treatments for CMT using cell culture, iPS cell, animal model, agents to suppress PMP22 expression, and read-through of stop codon methods are expected in the near features. In addition, development of surrogate markers, improvement of clinical trial design, establishment of nationwide diagnostic system, and assessment of natural history with international collaboration study must be done as soon as possible. CMT management manual, review of CMT research, open seminar for CMT, and genetic counseling are essential to improve the medical management for CMT. The collaboration among medical engineers, neurophysiologists, rehabilitation team, orthopedist, neurologists, genetic researchers and CMT patients and their families is of cardinal importance to achieve these studies for CMT.
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.
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.
