DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Charcot-Marie-Tooth disease type 2I — 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 2I 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 2i 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
The 2007 review notes that rapid advances in molecular genetics have highlighted the genetic complexity of Charcot-Marie-Tooth disease, but that the shift from a clinical to a molecular classification has not made the disease easier to understand. Different mutations in the same gene produce a range of phenotypes, and clinicians must rely on specific clinical and electrophysiological clues to direct genetic testing. No drug or treatment is discussed.
A 2008 study of a family with sex-linked CMT found no linkage 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 2009 case series describes three patients initially diagnosed with CMT who later developed eye signs and abdominal complaints, leading to a diagnosis of mitochondrial neurogastrointestinal encephalopathy (MNGIE). The authors advise that young mutation-negative CMT patients should be monitored for signs of MNGIE.
A 2019 report confirms the pathogenicity of the MFN2 mutation c.2222T>G (p.Leu741Trp) in a second family with dominantly inherited CMT, noting that the disease onset in this family was much later than in the previously reported family. The remaining abstracts cover orthotic management (1994) and surgical treatment of foot deformities (1985). In the surgical series of 12 feet, good results were obtained in 5 cases and bad results in 2, but the others could not be followed up.
No drug treatment for CMT2I is mentioned in any of these abstracts. What is missing is any clinical trial of a pharmacological intervention, any patient stratification by specific MFN2 mutation, and any funding for a repurposing study in this subtype.
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.
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.
AbstractCharcot-Marie tooth disease (CMT) is a heterogenous group of peripheral neuropathies caused by various genetic defects. Three cases of mitochondrial myopathy, neuropathy and gastrointestinal encephalopathy (MNGIE) which initially presented with a peripheral neuropathy resembling CMT are described here. The diagnosis in all three cases was made after they developed eye signs and abdominal complaints. Young patients with mutation negative CMT should be followed up to monitor for signs of MNGIE.
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.
JPO Journal of Prosthetics and Orthotics · 1994 · 1 citations
Orthotic Management of Charcot-Marie-Tooth
AbstractCharcot-Marie-Tooth Disease (CMT) is a neurological condition not commonly seen by orthotists. This article will review recent literature on histology, physical symptoms and classifications. Specific physical manifestations are discussed and illustrated. Four case studies are presented with each having a different clinical picture. Muscle grades and gait patterns as well as a knowledge of this disease's natural history will help practitioners to better provide successful orthotic management.
Surgical treatment of foot deformities in Charcot-Marie-Tooth disease
AbstractOut of 15 cases in which Charcot-Marie-Tooth disease was detected, a total of 19 operations were performed in 12 feet. Lambrinudi type of triple arthrodesis was performend an 15, achilloplasty on 8, and posterior capsulotomy on 2. The cases have been followed up for 4-20 years. Last controls could only be effected in 7 cases, while the others could not be followed. Good results were obtained in 5 and bad results in 2 cases.
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.
