DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for axonal neuropathy — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAxonal neuropathy maps to a 7-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 axonal neuropathy 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
mitofusin 2 (MFN2) — MFN2 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6JFK · 1.997 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
In 2008, three individuals with severe early-onset axonal neuropathy carried either homozygous or compound heterozygous mutations in the MFN2 gene. All of their parents, who carried a single heterozygous MFN2 mutation, were either asymptomatic or only mildly symptomatic, with some showing signs of peripheral neuropathy and two having hearing problems. The authors concluded that the severe form can appear recessively inherited but that the minimal phenotype in parents suggests a semi-dominant mechanism.
A 2011 review noted that more than ten genes causing dominantly and recessively inherited axonal Charcot–Marie–Tooth disease had been identified over the previous decade. Many of these genes encode ubiquitously expressed proteins. The review stated that animal and cellular models had been created and that the identification of these genetic causes had provided information about disease mechanisms relevant beyond axonal CMT, including sensory neuropathies and motor neuron disorders. Therapeutic strategies for some of these were mentioned as being provided, but no specific drug or clinical trial results were described.
A 2011 pilot study used routine median nerve ultrasonography to try to distinguish between 14 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 14 patients with sensory axonal neuropathy (SAN). The largest measured median nerve thickness was significantly greater in CIDP patients (P = 0.014), and a cut-off value gave a sensitivity of 57.1% for CIDP and a specificity of 92.9% against SAN. The authors noted that these findings require confirmation in larger, adequately designed studies evaluating other nerves and sites, including healthy controls, and accounting for interrater and equipment variability.
What remains missing for axonal neuropathy is any proven drug therapy from these abstracts. The genetic mechanisms are better understood, but no clinical trial data for a specific treatment are reported. Larger, properly controlled diagnostic studies are needed before ultrasonography can be used routinely. No patient stratification strategy or funding for a repurposing trial is described.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2008 · 112 citations
Severe early-onset axonal neuropathy with homozygous and compound heterozygous <i>MFN2</i> mutations
AbstractOBJECTIVE: Severe early-onset axonal neuropathy (SEOAN) is a heterogeneous phenotype first delineated by Ouvrier et al., characterized by progressive axonal degeneration with gait problems often progressing to wheelchair requirement and later respiratory involvement. Most cases are sporadic single cases. Some have heterozygous mitofusin 2 (MFN2) mutations, many of which are de novo dominant mutations. The aim of this study was to investigate the mode of inheritance in three individuals with severe early-onset axonal neuropathy and homozygous or compound heterozygous MFN2 mutations. METHODS: The clinical and molecular findings in the parents of three individuals with SEOAN with homozygous or compound heterozygous MFN2 mutations were examined. RESULTS: All parents were asymptomatic or mildly symptomatic with some signs of peripheral neuropathy indicating a minimal phenotype. Two had hearing problems. All parents carried the relevant single base (heterozygous) MFN2 variations. CONCLUSION: Severe early-onset axonal neuropathy due to MFN2 mutations can present as an apparently recessively inherited neuropathy but the minimal phenotype in the parents suggests a semi-dominant mechanism.
Current Opinion in Neurology · 2011 · 41 citations
Axonal Charcot–Marie–Tooth disease
AbstractPURPOSE OF REVIEW: The aim is to specify the genetic causes of dominantly and recessively inherited axonal forms of Charcot-Marie-Tooth disease (CMT) and review the biological basis for these disorders. RECENT FINDINGS: More than 10 genes that cause axonal CMT have been identified over the past decade. Many of these genes express proteins that are ubiquitously expressed. Clinical phenotypes of many of these disorders are being studied and animal and cellular models of these neuropathies have been created. SUMMARY: Identification of these new genetic causes of axonal neuropathy has not only been important for patients and their families but it has also provided exciting new information about disease mechanisms involved in neuronal degeneration. These mechanisms extend beyond the field of axonal CMT and have relevance to sensory neuropathies and motor neuron disorders. Therapeutic strategies for some of these are also provided. We hope that this review will be of interest to clinicians and scientists interested in axonal forms of CMT.
Median nerve ultrasonography in distinguishing neuropathy sub-types: a pilot study
AbstractBACKGROUND: The diagnostic potential of ultrasonography (US) in polyneuropathy has been studied rarely, with complex measurement/correction techniques. Whether US may be useful in clinical practice remains uncertain. MATERIALS AND METHODS: We aimed to ascertain the value of US, as performed routinely at our institution, in differentiating neuropathy sub-types. We prospectively studied 14 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 14 patients with sensory axonal neuropathy (SAN). Median nerves were studied bilaterally at wrist and forearm by a radiologist blinded to the neuropathy sub-type. Nerve width (medial to lateral diameter), thickness (anterior to posterior diameter) and cross-sectional area were compared in between patient groups and anatomical sites. Optimal cut-off values were determined using receiver operating characteristic (ROC) curves. RESULTS: Largest measured median nerve thickness was significantly greater in patients with CIDP (P = 0.014), and ROC curve analysis indicated a cut-off offering a sensitivity of 57.1% for CIDP and specificity of 92.9% vs SAN. Nerves were wider and had larger cross-sectional areas, but were not thicker, at wrist compared to forearm in both patient groups. There was an equal prevalence in both patients with CIDP and SAN, of increased median nerve wrist-to-forearm area ratio, compatible with sub-clinical carpal tunnel syndrome. CONCLUSION: This prospective, blinded, pilot study is the first to indicate the diagnostic potential of US, as performed routinely, in distinguishing between acquired demyelinating and axonal neuropathy. These findings now require confirmation in larger, adequately designed studies, evaluating other nerves/nerve sites, assessing healthy controls and taking into account interrater and equipment variabilities.
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.
