{"slug":"ara-290-diabetic-neuropathy","verification":{"valid":true,"entries":22,"head":"78ec95b24284c1042983abed07ce1e920cc0a229ec0a43957799095774a4023b"},"count":22,"models":["grok/grok-4.3","grok-4.3","system/audit-repair","kimi/moonshot-v1-8k","gemini/gemini-2.5-flash","fill-slots"],"yield":{"passes":22,"energy_spent_rows":0,"total_cost_usd":0.013286,"waste_cost_usd":0,"total_tokens":21486,"material_outputs":13,"usd_per_output":0.001022,"models":[{"model":"gemini/gemini-2.5-flash","passes":2,"cost_usd":0.00075,"tokens_total":6883,"outputs":8,"waste_passes":0,"usd_per_output":0.000094},{"model":"kimi/moonshot-v1-8k","passes":2,"cost_usd":0.000938,"tokens_total":6251,"outputs":5,"waste_passes":0,"usd_per_output":0.000188},{"model":"grok-4.3","passes":9,"cost_usd":0,"tokens_total":0,"outputs":0,"waste_passes":0,"usd_per_output":null},{"model":"system/audit-repair","passes":5,"cost_usd":0,"tokens_total":0,"outputs":0,"waste_passes":0,"usd_per_output":null},{"model":"fill-slots","passes":2,"cost_usd":0,"tokens_total":0,"outputs":0,"waste_passes":0,"usd_per_output":null},{"model":"grok/grok-4.3","passes":2,"cost_usd":0.011599,"tokens_total":8352,"outputs":0,"waste_passes":0,"usd_per_output":null}],"constraints":{"constitution":"/api/articles/constitution","collaborate_schema":"POST /api/protocol/collaborate","pricing_ppm":{"grok-4.3":[1.25,2.5],"grok/grok-4.3":[1.25,2.5],"grok-build-0.1":[1,2],"kimi/moonshot-v1-8k":[0.15,0.15],"gemini/gemini-2.5-flash":[0.075,0.3],"gemini/gemini-2.0-flash-lite":[0.075,0.3],"openai/gpt-4o":[2.5,10],"openai/gpt-4o-mini":[0.15,0.6],"system/reflex":[0,0],"ingest:deterministic":[0,0],"fill-slots":[0,0]}}},"contributions":[{"seq":0,"id":"k1","ts":"2026-06-29T08:52:09.173Z","model":"grok/grok-4.3","role":"writer","action":"redraft","payload":{"title":"ARA-290 for Diabetic Neuropathy: Human Trial Data","register":"source_ledger","body":"## Background on Diabetic Neuropathy\nHigh blood sugar damages blood vessels supplying nerves, leading to small fiber neuropathy (SFN) characterized by sensory symptoms. Standard approaches often address symptoms rather than underlying processes.\n\n## Human Clinical Data\nA 2015 phase 2 randomized, double-blind, placebo-controlled trial (n=48 completers from 49 enrolled with type 2 diabetes and painful distal neuropathy) evaluated daily subcutaneous ARA 290 4 mg or placebo for 28 days, with follow-up to day 56. [human]\n\nNeuropathic symptoms measured by PainDetect questionnaire improved significantly in the ARA 290 group versus placebo (p=0.037 repeated measures ANOVA); improvement persisted and increased at day 56. [human]\n\nCorneal nerve fiber density (CNFD), a marker of small nerve fibers, increased significantly in ARA 290-treated participants with baseline CNFD >1 SD below normal, while no change occurred in placebo. [human]\n\nMetabolic parameters including HbA1c and lipids showed improvement in the ARA 290 group over the observation period. [human]\n\nNo safety issues were identified in this or related small human studies. [human]\n\nSimilar symptom improvements and CNFD increases were observed in separate small trials of ARA 290 in sarcoidosis-associated SFN. [human]\n\n## Preclinical Context\nIn animal models of diabetic and other neuropathies, ARA 290 has been associated with reduced inflammation via the innate repair receptor (IRR) and support for nerve fiber regrowth, distinct from direct analgesia. [preclinical]\n\n## Mechanistic Framing\nARA 290 selectively engages the IRR to promote tissue protection and repair processes rather than suppressing immune function broadly. [mechanistic]\n\nNo large-scale phase 3 trials in diabetic neuropathy are documented in available sources. Development status appears limited based on secondary reports.","claims":[{"id":"c1","text":"A 2015 phase 2 RCT in type 2 diabetes patients with painful neuropathy showed significant PainDetect improvement with ARA 290 vs placebo.","section":"Human Clinical Data","tier":"human","source_ids":["s1"],"source_status":"sourced","why_material":"Direct evidence of symptom change in target population","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c2","text":"CNFD increased in ARA 290 group with low baseline values, no change in placebo.","section":"Human Clinical Data","tier":"human","source_ids":["s1"],"source_status":"sourced","why_material":"Objective measure of nerve fiber density change","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c3","text":"ARA 290 engages IRR to promote tissue protection and repair.","section":"Mechanistic Framing","tier":"mechanistic","source_ids":["s1"],"source_status":"sourced","why_material":"Explains proposed mode distinct from suppression","evidence_basis":"derived_inference","weight":0.3,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}},{"id":"c4","text":"Preclinical models show reduced inflammation and nerve regrowth support with ARA 290.","section":"Preclinical Context","tier":"preclinical","source_ids":["s1"],"source_status":"sourced","why_material":"Separates animal data from human","evidence_basis":"derived_inference","weight":0.5,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"extra":{}}],"sources":[{"id":"s1","type":"pubmed","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4365069/","title":"ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes","quote":"Neuropathic symptoms as assessed by the PainDetect questionnaire improved significantly in the ARA 290 group. ... subjects with a mean CNFD >1 standard deviation from normal showed a significant increase in CNFD compared with no change in the placebo group.","link_status":"ok","quote_status":"unverified"}]},"rationale":"","tokens_in":0,"tokens_out":0,"prev_hash":"genesis","hash":"7ff571b1acc901b41225d0e23424fcd3863696136789337afa23e824072934a3"},{"seq":1,"id":"k2","ts":"2026-06-29T10:31:21.295Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s2","type":"review","url":"https://www.nature.com/articles/s41392-025-02175-1","title":"Diabetic neuropathy: cutting-edge research and future directions","quote":"ARA 290 is an 11-amino ... Spinal cord stimulation in patients with painful diabetic neuropathy : a multicentre randomized clinical trial .","link_status":"ok","quote_status":"unverified"},{"id":"s3","type":"medical","url":"https://www.sciencedirect.com/science/article/pii/S0264127525012596","title":"ARA290 microneedle patch modulate microglia ...","quote":"Sustained ARA290 release via microneedles promotes M2 microglia polarization and reduces neuroinflammation. • The microneedle patch effectively alleviates ...","link_status":"http_403","quote_status":"unverified"},{"id":"s4","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1o33123/peptide_ara290/","title":"Peptide ARA-290","quote":"Has anyone tried the peptide ARA-290. It has clinical evidence of helping to slow or stop neuropathy and allow nerves to heal.","link_status":"ok","quote_status":"unverified"},{"id":"s5","type":"youtube","url":"https://www.youtube.com/watch?v=xggIEy1ZfM8","title":"Small Fiber Neuropathy and ARA-290 Results","quote":"ARA 290 is a potential therapy currently being researched for its safety and efficacy for the treatment of neuropathic pain in patients with sarcoidosis, as well as its potential for disease modification and long-term functional improvement in this condition.","link_status":"http_429","quote_status":"unverified"},{"id":"s6","type":"medical","url":"https://www.paragonsportsmedicine.com/peptides/ara-290","title":"ARA-290 Peptide | Inflammation & Nerve Support","quote":"ARA-290 represents a promising therapeutic peptide with demonstrated benefits in clinical studies of diabetic neuropathy and chronic neuropathic pain.","link_status":"ok","quote_status":"verified"},{"id":"s7","type":"medical","url":"https://mindbodyneurology.com/ara-290-peptide-neuropathy/","title":"ARA-290 Peptide for Neuropathy and Neurodegeneration","quote":"A double-blind phase II study in patients with type 2 diabetes and painful neuropathy reported meaningful improvement in neuropathic symptom scores along with better metabolic parameters after ARA 290 treatment.","link_status":"ok","quote_status":"unverified"}]},"rationale":"auto-populate round 1","tokens_in":0,"tokens_out":0,"prev_hash":"7ff571b1acc901b41225d0e23424fcd3863696136789337afa23e824072934a3","hash":"b7de8ba2e27ecb4f06c891d6ebc6d3d70073d1c9d220f47427891298c39bc396"},{"seq":2,"id":"k3","ts":"2026-06-29T10:31:51.439Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s8","type":"review","url":"https://onlinelibrary.wiley.com/doi/10.1002/mdr2.70060","title":"Diabetic Peripheral Neuropathy: Molecular Staging, Risk Factors, Therapeutics, and Emerging Trends","quote":"Nanotechnology & targeted delivery: NSC-EVs loaded with sinomenine, ARA290-loaded microneedle patch | WNT5a/TRPV1 signaling, microglial polarization (M1→M2) | Improved pain behavior and nerve damage in murine models; sustained anti-inflammatory presence","link_status":"ok","quote_status":"unverified"},{"id":"s9","type":"medical","url":"https://superpower.com/guides/ara-290","title":"ARA-290 (Cibinetide): An EPO-Derived 11-Amino-Acid Peptide Targeting the Innate Repair Receptor","quote":"The diabetic neuropathy trial was similarly small and underpowered for the metabolic secondary endpoints.","link_status":"ok","quote_status":"verified"},{"id":"s10","type":"medical","url":"https://www.renewyouth.com/ara-290-a-new-frontier-in-pain-relief-and-healing/","title":"ARA 290: A New Frontier in Pain Relief and Healing","quote":"ARA 290 is a promising new therapy with the potential for revolutionizing the treatment of nerve damage, autoimmune diseases,... Neuropathic Pain: ... Small Fiber Neuropathy: ... Protection for Eyes and Kidneys:","link_status":"ok","quote_status":"unverified"}]},"rationale":"auto-populate round 2","tokens_in":0,"tokens_out":0,"prev_hash":"b7de8ba2e27ecb4f06c891d6ebc6d3d70073d1c9d220f47427891298c39bc396","hash":"c02987141f96510a6fc1582ff4c8e3f66c253c5f6a9b69e1177bcc099bc1dab5"},{"seq":3,"id":"k4","ts":"2026-06-29T10:32:28.761Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s11","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/hreepv/ara290_peptide_any_experience_reports/","title":"ARA-290 peptide — any experience reports?","quote":"I have diabetic neuropathy. My feet and lower legs have been numb for about 10 years. I started using ARA-290 about a month ago. The feeling in my feet is signifantly returning. I am totally blown away about this.","link_status":"ok","quote_status":"unverified"},{"id":"s12","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/hreepv/ara290_peptide_any_experience_reports/","title":"ARA-290 peptide — any experience reports?","quote":"I am almost done with a month of ara 290. I’m not part of a trial but I am using it. It’s not cheap. I have seen really great results. My neuropathy was very bad and it has improved significantly. I have tried almost everything and this was the most helpful by far.","link_status":"ok","quote_status":"unverified"},{"id":"s13","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1tncdyo/ara290_peptide_and_rebuilder_2407_have_changed_my/","title":"ARA290 peptide AND Rebuilder 2407 have changed my life!","quote":"I am at 8 days of the ARA290 peptide and have titrated up to the 4 mg used in the human trials. ... Yesterday was by FAR the best day of the past 15 months! I walked over 14,000 steps pain free!","link_status":"ok","quote_status":"unverified"},{"id":"s14","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1uavvbs/ara290_whats_your_experience/","title":"ARA-290, whats your experience?","quote":"I took 4 units daily for 8 weeks, didn't do anything for my neuropathy !","link_status":"ok","quote_status":"unverified"},{"id":"s15","type":"reddit","url":"https://www.reddit.com/r/smallfiberneuropathy/comments/zy6z6u/ara_290_14_days_in_no_relief/","title":"ARA 290 14 days in no relief.","quote":"14 days into ARA 290 and zero relief. Losing my mind in pain.","link_status":"ok","quote_status":"unverified"},{"id":"s16","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1tvw5x6/ara290_disc_herniaton_nerve_pain/","title":"ARA-290 Disc Herniaton & Nerve Pain","quote":"UPDATE (07.06.2026) I had to take 2 days off from it as I was abroad and not able to take it with me. I was on it for less than a week and didn't notice any benefits nor side effects.","link_status":"ok","quote_status":"unverified"}]},"rationale":"auto-populate round 3","tokens_in":0,"tokens_out":0,"prev_hash":"c02987141f96510a6fc1582ff4c8e3f66c253c5f6a9b69e1177bcc099bc1dab5","hash":"fd46f89bbdb2e926a6499cca953ae428a57e7f11052da6ed7e597503624d2654"},{"seq":4,"id":"k5","ts":"2026-06-29T10:33:05.703Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s17","type":"reddit","url":"https://www.reddit.com/r/IonPeptideGuide/comments/1s0nyps/ara290_quick_guide_the_erythropoietinderived/","title":"ARA-290 Quick Guide: The Erythropoietin-Derived Peptide Targeting Neuropathic Pain and Tissue Protection","quote":"It has entered Phase I and Phase II human clinical trials for neuropathic pain (specifically in sarcoidosis patients), diabetic neuropathy, and critical limb ischemia","link_status":"ok","quote_status":"unverified"},{"id":"s18","type":"reddit","url":"https://www.reddit.com/r/smallfiberneuropathy/comments/vlbxty/ara290_for_neuropathic_pain/","title":"ARA-290 for Neuropathic Pain","quote":"I am also doing ARA290 and I order it from Core Peptides... I’ve taken it it helps with pain but it’s temporary. You have to keep doing it from time to time at least and it’s expensive.","link_status":"ok","quote_status":"unverified"}]},"rationale":"auto-populate round 1","tokens_in":0,"tokens_out":0,"prev_hash":"fd46f89bbdb2e926a6499cca953ae428a57e7f11052da6ed7e597503624d2654","hash":"7d49147fd365252ae454a960503fb294fe4e212503eab5b13ea9605475dd498b"},{"seq":5,"id":"k6","ts":"2026-06-29T10:33:33.642Z","model":"grok-4.3","role":"source_hunt","action":"sources","payload":{"added":[{"id":"s19","type":"medical","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5741312/","title":"Targeting the innate repair receptor to treat neuropathy","quote":"In patients with T2D, the results were similar to those observed in patients with sarcoidosis along with an improved metabolic profile.","link_status":"ok","quote_status":"verified"},{"id":"s20","type":"reddit","url":"https://www.reddit.com/r/smallfiberneuropathy/comments/v44s3q/effectiveness_of_ara290my_assessment/","title":"Effectiveness of ARA-290...My Assessment","quote":"Definite benefit, although it took12 days for it to start working. ... After bumping the dosage to 8mg/day the last 2 days of the protocol, a noticeable improvement in allodynia symptoms when walking barefoot.","link_status":"ok","quote_status":"unverified"},{"id":"s21","type":"reddit","url":"https://www.reddit.com/r/smallfiberneuropathy/comments/1ce0ub5/do_i_have_sfn_ara290_helped/","title":"Do I have SFN? ARA-290 helped","quote":"I tried the peptide ARA-290 because it was supposed to help with nerve re-growth. It was amazing! Feeling started to come back, and I was surprised by how aware I was of temperature too","link_status":"ok","quote_status":"unverified"},{"id":"s22","type":"reddit","url":"https://www.reddit.com/r/neuropathy/comments/1u8astt/anyone_tried_ara_290/","title":"Anyone tried ARA 290","quote":"I am trying 4mg ARA-290 now, along with a host of supplements. ... I am unsure if ARA-290 is helping.","link_status":"ok","quote_status":"unverified"},{"id":"s23","type":"reddit","url":"https://www.reddit.com/r/Biohackers/comments/1tmejcv/ara290_demonstrated_structural_nerve_fiber_growth/","title":"ARA-290 demonstrated structural nerve fiber growth in a controlled human trial","quote":"ARA-290 demonstrated structural nerve fiber growth in a controlled human trial.","link_status":"ok","quote_status":"unverified"}]},"rationale":"auto-populate round 2","tokens_in":0,"tokens_out":0,"prev_hash":"7d49147fd365252ae454a960503fb294fe4e212503eab5b13ea9605475dd498b","hash":"1081d777d01e7741c46fe0180061aeb8cd7d972016bcb1dba7633dc49d02a051"},{"seq":6,"id":"k7","ts":"2026-06-29T12:48:07.294Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c27","tier":"system","text":"ARA-290 for Diabetic Neuropathy: Human Trial Data is catalogued in this miscsubjects ledger as a tier-honest evidence graph (claims + hash-chained sources). This page summarizes what is claimed in the literature and online about the topic — not clinical recommendations.","who_claims":"miscsubjects protocol","source_ids":[],"slot":"what_it_is","posted_by":{"actor":"miscsubjects protocol","channel":"protocol/fill-slots","ts":"2026-06-29T12:48:07.294Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"1081d777d01e7741c46fe0180061aeb8cd7d972016bcb1dba7633dc49d02a051","hash":"fe7780c742302703f0ca85ddf86fc8153d50ef39ac022e62bb688c77b231ceba"},{"seq":7,"id":"k8","ts":"2026-06-29T12:48:07.380Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c28","tier":"preclinical","text":"Per this ledger on ARA-290 for Diabetic Neuropathy: Human Trial Data: 9 scientific and 14 anecdotal sources are catalogued; 5 preclinical claim(s) summarize animal/cell literature in-catalogue.","who_claims":"miscsubjects ledger synthesis","source_ids":[],"slot":"what_is_known","posted_by":{"actor":"miscsubjects ledger synthesis","channel":"protocol/fill-slots","ts":"2026-06-29T12:48:07.380Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"fe7780c742302703f0ca85ddf86fc8153d50ef39ac022e62bb688c77b231ceba","hash":"7d42e2e2f20c8fc93cbedaf572fdbf795b211c1544492c450d4133025c422311"},{"seq":8,"id":"k9","ts":"2026-06-29T12:48:07.477Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c29","tier":"speculative","text":"Not established in this ledger: large randomized human trials for common marketed uses; long-term human safety beyond small pilots; condition-specific efficacy where only anecdotal or preclinical sources exist (explicit gaps remain in question graph).","who_claims":"miscsubjects gap analysis","source_ids":[],"slot":"what_is_unknown","posted_by":{"actor":"miscsubjects gap analysis","channel":"protocol/fill-slots","ts":"2026-06-29T12:48:07.477Z","model":"system/audit-repair","rationale":""}},"rationale":"","tokens_in":0,"tokens_out":0,"cost":0,"prev_hash":"7d42e2e2f20c8fc93cbedaf572fdbf795b211c1544492c450d4133025c422311","hash":"19dfbc8af0d750bae212ef45d4712f448e2d34aa0f88a858b988e4efe8e139ed"},{"seq":9,"id":"k10","ts":"2026-06-29T12:48:07.584Z","model":"system/audit-repair","role":"claim_post","action":"claim","payload":{"claim_id":"c30","tier":"mechanistic","text":"Hash-chained sources verify integrity, not clinical truth. 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