DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for neuropathy — screening already-approved drugs against its 40-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNeuropathy maps to a 40-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 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
phosphoglycerate dehydrogenase (PHGDH) — PHGDH 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 1~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6RJ3 · 1.42 Å · ligand 4-[(1~{R})-1-[(2-methyl-5-phenyl-pyrazol-3-yl)carbonylamino]ethyl]benzoic acid (K58). Experimental structure, not a prediction.
What the evidence adds up to
A 2019 study of anti-neurofascin autoantibodies identified two distinct clinical phenotypes among five patients. Two patients had the known subacute severe sensorimotor neuropathy with tremor associated with IgG4 antibodies against the paranodal isoform NF-155. Three other patients had a fulminant course with tetraplegia and almost locked-in syndrome, associated with IgG3 antibodies against the common Ig domain of all three neurofascin isoforms. The authors concluded that epitope and subclass play a major role in pathogenesis and severity, and should be determined to correctly classify patients, also in respect to possible differences in therapeutic response.
A 2007 review of painful neuropathy treatment stated that tricyclic antidepressants, gabapentin, major and minor opioids, pregabalin, and serotonin-noradrenaline-reuptake inhibitors have demonstrated efficacy. It noted disappointing results for memantine, mexiletine, topiramate, and lamotrigine. The review highlighted that most clinical trials focus only on diabetic neuropathy and postherpetic neuralgia, and that studies on polytherapy are insufficient, making evidence-based data hard to translate into clinical practice.
A 2020 review of Charcot-Marie-Tooth disease and other hereditary neuropathies reported that next-generation sequencing has greatly improved genetic diagnosis, and that a definitive molecular diagnosis affords patients improved care and counsel. It stated that emerging therapeutic approaches include small molecule chaperones, antisense oligonucleotides, RNA interference, and viral gene delivery therapies, with new therapies for hereditary transthyretin amyloidosis and Fabry disease discussed. For most inherited neuropathy categories, specific symptomatic management and family counselling remain the mainstays of therapy.
A 2017 study sequenced sodium channel genes in 457 patients from a neuropathy registry (278 idiopathic, 179 diabetic). It found a significant increase in the alternate allele frequency of the common variant p.V1073A and low-frequency variant p.S509P compared to European reference populations. The authors concluded that the likelihood of finding effective sodium channel 1.7 inhibitors in patients with peripheral neuropathy is unlikely, and that additional factors beyond previously reported disease mutations are more important for the development of painful neuropathy. What is still missing are large, adequately powered trials that stratify patients by genetic and autoantibody subtype, and studies that test polytherapy regimens for the heterogeneous conditions grouped under neuropathy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Anti–pan-neurofascin IgG3 as a marker of fulminant autoimmune neuropathy
AbstractOBJECTIVE: To identify and characterize patients with autoantibodies against different neurofascin (NF) isoforms. METHODS: Screening of a large cohort of patient sera for anti-NF autoantibodies by ELISA and further characterization by cell-based assays, epitope mapping, and complement binding assays. RESULTS: Two different clinical phenotypes became apparent in this study: The well-known clinical picture of subacute-onset severe sensorimotor neuropathy with tremor that is known to be associated with IgG4 autoantibodies against the paranodal isoform NF-155 was found in 2 patients. The second phenotype with a dramatic course of disease with tetraplegia and almost locked-in syndrome was associated with IgG3 autoantibodies against nodal and paranodal isoforms of NF in 3 patients. The epitope against which these autoantibodies were directed in this second phenotype was the common Ig domain found in all 3 NF isoforms. In contrast, anti-NF-155 IgG4 were directed against the NF-155-specific Fn3Fn4 domain. The description of a second phenotype of anti-NF-associated neuropathy is in line with some case reports of similar patients that were published in the last year. CONCLUSIONS: Our results indicate that anti-pan-NF-associated neuropathy differs from anti-NF-155-associated neuropathy, and epitope and subclass play a major role in the pathogenesis and severity of anti-NF-associated neuropathy and should be determined to correctly classify patients, also in respect to possible differences in therapeutic response.
Current Opinion in Neurology · 2007 · 71 citations
Treatment of painful neuropathy
AbstractPURPOSE OF REVIEW: With the aging of the population, treatment of painful neuropathies is becoming more and more important for neurological practice. This short review highlights recent findings and current problems. RECENT FINDINGS: In addition to tricyclic antidepressants and gabapentin, the reliability of which is established, some drugs have more recently been demonstrated to be efficacious: major and minor opioids, pregabalin, and serotonin-noradrenaline-reuptake inhibitors. In contrast, some other drugs have yielded disappointing results: memantine, mexiletine, topiramate, and - very recently - lamotrigine. Three main questions are currently being debated. Notwithstanding their proven efficacy, should opioids be used in chronic noncancer pain? In which patients should serotonin-noradrenaline-reuptake inhibitors be preferred to tricyclic antidepressants? What is the difference between pregabalin and gabapentin? The whole field suffers from important limitations that make evidence-based medical data hard to translate in clinical practice: most clinical trials were and still are focused on two conditions only (diabetic neuropathy and postherpetic neuralgia) and studies on polytherapy are insufficient. SUMMARY: A large variety of drugs are being tried in the treatment of painful neuropathy. Neurologists now have a wide choice. Recent publications can help in choosing the best treatment course.
CONTINUUM Lifelong Learning in Neurology · 2020 · 63 citations
Charcot-Marie-Tooth Disease and Other Hereditary Neuropathies
AbstractPURPOSE OF REVIEW: This article provides an overview of Charcot-Marie-Tooth disease (CMT) and other inherited neuropathies. These disorders encompass a broad spectrum with variable motor, sensory, autonomic, and other organ system involvement. Considerable overlap exists, both phenotypically and genetically, among these separate categories, all eventually exhibiting axonal injury and neurologic impairment. Depending on the specific neural and non-neural localizations, patients experience varying morbidity and mortality. Neurologic evaluations, including neurophysiologic testing, can help diagnose and predict patient disabilities. Diagnosis is often complex, especially when genetic and acquired components overlap. RECENT FINDINGS: Next-generation sequencing has greatly improved genetic diagnosis, with many third-party reimbursement parties now embracing phenotype-based panel evaluations. Through the advent of comprehensive gene panels, symptoms previously labeled as idiopathic or atypical now have a better chance to receive a specific diagnosis. A definitive molecular diagnosis affords patients improved care and counsel. The new classification scheme for inherited neuropathies emphasizes the causal gene names. A specific genetic diagnosis is important as considerable advances are being made in gene-specific therapeutics. Emerging therapeutic approaches include small molecule chaperones, antisense oligonucleotides, RNA interference, and viral gene delivery therapies. New therapies for hereditary transthyretin amyloidosis and Fabry disease are discussed. SUMMARY: Comprehensive genetic testing through a next-generation sequencing approach is simplifying diagnostic algorithms and affords significantly improved decision-making processes in neuropathy care. Genetic diagnosis is essential for pathogenic understanding and for gene therapy development. Gene-targeted therapies have begun entering the clinic. Currently, for most inherited neuropathy categories, specific symptomatic management and family counseling remain the mainstays of therapy.
Neurology Genetics · 2017 · 38 citations · open access
Na<sub>V</sub>channel variants in patients with painful and nonpainful peripheral neuropathy
AbstractOBJECTIVE: 1.9) in patients with painful and nonpainful peripheral neuropathy. METHODS: Next-generation sequencing was performed on 457 patient DNA samples provided by the Peripheral Neuropathy Research Registry (PNRR). The patient diagnosis was as follows: 278 idiopathic peripheral neuropathy (67% painful and 33% nonpainful) and 179 diabetic distal polyneuropathy (77% painful and 23% nonpainful). RESULTS: , there was a significant increase in the alternate allele frequency of the common variant p.V1073A and low-frequency variant pS509P in PNRR patients compared with EVS-EA and the 1000 Genomes European reference populations. CONCLUSIONS: 1.7 inhibitors in patients with peripheral neuropathy is unlikely and that additional factors, beyond expression of previously reported disease "mutations," are more important for the development of painful neuropathy than previously discussed.
Journal of Addiction Medicine and Therapeutic Science · 2016 · 1 citations · open access
Role of Duloxetine as Adjuvant in Chemotherapy Induced Peripheral Neuropathic Pain-An Update
AbstractChemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of many anticancer drugs such as platinum compounds, antitubulins (taxanes and vinca alkaloids), bortezomib and thalidomide [1]. CIPN may manifest as sensory symptoms in hands and feet, typically in a “glove and stocking” pattern; pain, numbness, tingling etc; or motor symptoms such as weakness, deficits in the cranial nerve or autonomic neuropathy [2]. Various pharmacological agents have been evaluated for management of CIPN and have been reported to have variable effects.
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.
