DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for diabetic neuropathy — screening already-approved drugs against its 41-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDiabetic neuropathy maps to a 41-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 diabetic 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
glutamate ionotropic receptor AMPA type subunit 2 (GRIA2) — GRIA2 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 gludrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3RN8 · 1.7 Å · ligand GLUTAMIC ACID (GLU). Experimental structure, not a prediction.
What the evidence adds up to
A 2020 review catalogues biomarkers implicated in diabetic neuropathy, including inflammatory markers such as MCP-1, VEGF, TRPV1, and NF-κB; oxidative markers such as adiponectin and NFE2L2; enzymes such as NADPH, ceruloplasmin, HO-1, DPP-4, and PARP α; and miscellaneous markers such as SIRT1, caveolin 1, MALAT1, and microRNA. The authors state that all these biomarkers have a significant role in the pathogenesis of diabetic neuropathy and can be considered potential targets for new drug discovery. No clinical trial data are presented in that paper.
A 1996 review of clinical trials for diabetic polyneuropathy states plainly that the results of these trials have in general been disappointing. The authors discuss selection criteria, efficacy endpoints, trial duration, and data analysis, and offer suggestions based on past experience to improve trial design and execution. A 1998 review notes that symptomatic peripheral neuropathy affects up to 62% of Americans with diabetes, that numerous pharmacologic agents have been used but all can be associated with adverse side effects, and that subsensory electrical stimulation may be preferred because it is equally effective and has a more favourable safety profile. A 2003 review is blunt: despite much data from preclinical models, many interventions reaching phase III clinical trials have failed to prove effective, and there is no evidence-based and effective treatment for human diabetic neuropathy.
A 2024 review observes that the exact mechanism by which diabetic neuropathy develops is still not fully known, and that progressing neuropathy may occur despite a persistently favourable metabolic status in some patients, while an unfavourable metabolic status is not always associated with significant neuropathy in others, which the authors attribute largely to genetic differences. They call for more personalised approaches that take individual genetic profiles into account. What is still missing is a clear, validated pathogenetic model that translates into effective phase III trials; adequate patient stratification by genetic or biomarker profile; and the funding and trial infrastructure to test such stratified approaches rather than repeating the pattern of disappointing large-scale trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
A randomized, placebo-controlled study of oxcarbazepine in painful diabetic neuropathy
AbstractOBJECTIVES: To evaluate the efficacy and safety of oxcarbazepine (1200 mg/day) in patients with painful diabetic neuropathy in a multicentre, double-blind, placebo-controlled, 16-week study. METHODS: A total of 141 patients were randomized to oxcarbazepine (1200 mg/day) (n = 71) or placebo (n = 70). The primary efficacy variable was the change in mean visual analogue scale (VAS) score from baseline to the last week the patient participated in the study. RESULTS: The reduction in mean VAS score from baseline to the last study week was similar between the oxcarbazepine and placebo groups. The majority of adverse events (most of which first occurred during titration) were mild to moderate in severity and resolved over the course of the study. CONCLUSIONS: In this study, no statistically significant difference in therapeutic effect was observed between oxcarbazepine (1200 mg/day) and placebo. However, further studies are necessary to assess the effective dose range of oxcarbazepine in the treatment of painful diabetic neuropathy.
Archives of Physiology and Biochemistry · 2020 · 38 citations
Biomarkers in diabetic neuropathy
AbstractCONTEXT: The prevalence of diabetic neuropathy is drastically increasing in the world. To halt the progression of diabetic neuropathy, there is an unmet need to have potential biomarkers for the diagnosis and new drug discovery. OBJECTIVE: To study various biomarkers involved in the pathogenesis of diabetic neuropathy. METHODS: The literature was searched with the help of various scientific databases and resources like PubMed, ProQuest, Scopus, and Google scholar from the year 1976 to 2020. RESULTS: Biomarkers of diabetic neuropathy are categorised as inflammatory biomarkers such as MCP-1, VEGF, TRPV1, NF-κB; oxidative biomarkers such as adiponectin, NFE2L2; enzyme biomarkers like NADPH, ceruloplasmin, HO-1, DPP-4, PARP α; miscellaneous biomarkers such as SIRT1, caveolin 1, MALAT1, and microRNA. All biomarkers have a significant role in the pathogenesis of diabetic neuropathy. CONCLUSION: These biomarkers have a potential role in the progression of diabetic neuropathy and can be considered as potential targets for new drug discovery.
Design of Controlled Clinical Trials for Diabetic Polyneuropathy
AbstractDiabetic neuropathy is a common and debilitating complication of diabetes mellitus associated with high health costs. In recent years several clinical trials have been undertaken to test the efficacy of drug intervention in this disorder. The results of these trials have in general been disappointing. In this review we discuss selection criteria, efficacy endpoints, duration of clinical trials, and data collection and analyses. We offer suggestions based on past experiences that might improve trial design and execution in order to achieve improved results from treatment of this silent but common disorder.
Pathophysiology and Treatment of Painful Diabetic Neuropathy of the Lower Extremity
AbstractBACKGROUND: Symptomatic peripheral neuropathy is the most common complication of diabetes mellitus, affecting up to 62% of Americans with diabetes. METHODS: We reviewed the literature using the National Library of Medicine's MEDLINE search service. In total, we reviewed 54 articles. RESULTS: Hyperglycemia leads to increased activity in the polyol pathway in nerve cells; this ultimately results in abnormal nerve function. Numerous pharmacologic agents have been used to treat symptomatic peripheral neuropathy, but all of these drugs can be associated with adverse side effects. Recent work has indicated that subsensory electrical stimulation may be preferred to pharmacotherapy, since it is equally effective and has a more favorable safety profile. CONCLUSION: Although the pathophysiology of diabetic neuropathy is well understood, treatment of the symptoms associated with this condition can be challenging. Additional research is needed to reveal a safe and effective treatment for this debilitating sequela of diabetes mellitus.
The Korean Journal of Internal Medicine · 1999 · 13 citations · open access
Effect of Cilostazol on the Neuropathies of Streptozotocin - induced Diabetic Rats
AbstractOBJECTIVES: This study examined the effect of cilostazol, a potent phosphodiesterase inhibitor, on the progression of neuropathies associated with streptozotocin-induced diabetes mellitus in Sprague-Dawley rats. METHODS: Eight weeks after streptozotocin treatment, a pelleted diet containing 0.03% cilostazol (15 mg/kg body weight) was given for four weeks. Body weight, blood glucose level, motor nerve conduction velocity (MNCV), myelinated fiber density and size distribution of sciatic nerves were compared between age-matched normal rats (Group 1), control diabetic rats (Group 2) and cilostazol-treated diabetic rats (Group 3). RESULTS: Body weight was significantly reduced and blood glucose level was significantly increased in diabetic rats (Group 2 and 3) compared to normal rats. MNCV and cAMP content of sciatic nerves were significantly reduced in diabetic rats 12 weeks after streptozotocin treatment. Myelinated fiber size and density were also significantly reduced, and thickening of the capillary walls and duplication of the basement membranes of the endoneural vessels were observed in the diabetic rats. Whereas both body weight and blood glucose level of Group 3 did not differ significantly from those of Group 2, cilostazol treatment significantly increased MNCV and cAMP content of sciatic nerves in Group 3 but not to the levels observed in Group 1. MNCV positively correlated with cAMP content of sciatic nerves (r = 0.86; p < 0.001). Cilostazol treatment not only restored myelinated fiber density and size distribution but reversed some of the vascular abnormalities. CONCLUSION: These findings suggest that a reduced cAMP content in motor nerves may be involved in the development of diabetic neuropathy, and that cilostazol may prevent the progression of diabetic neuropathy by restoring functional impairment and morphological changes of peripheral nerves.
International Journal of Molecular Sciences · 2024 · 6 citations · open access
Genetic Variants Influence the Development of Diabetic Neuropathy
AbstractThe exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background-in particular, accelerated progress is being made in understanding molecular biological mechanisms-some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles.
The British Journal of Diabetes · 2003 · 2 citations
Failure to define the pathogenesis and treatment of human diabetic neuropathy
AbstractThe clinical manifestations, underlying pathology and aetiology of human diabetic neuropathy are varied and complex. Much data has been generated from preclinical models to provide a conceptual framework for the cause and treatment of human diabetic neuropathy. Despite this there remains much debate and controversy on the pathophysiology of the condition. Furthermore, many of the interventions reaching phase III clinical trials have failed to prove effective. To date we have no evidence-based and effective treatment(s) for human diabetic neuropathy.
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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