ARA-290 (Cibinetide)
ARA-290 (Cibinetide) scored 5.8 / 10 (👍 Worth trying) on the BioHarmony scale as a Substance → Peptide → Other Peptide.
ARA-290 (cibinetide) is an EPO-derived peptide that activates the innate repair receptor to regrow small nerve fibers without EPO's blood effects. Corneal nerve fiber area rose significantly at 4 mg per day, per Culver 2017, but it never passed Phase 2 and is grey-market only.
What is ARA-290 (Cibinetide)?
ARA-290 (cibinetide) is an 11-amino-acid peptide built from the helix-B region of erythropoietin, and it lands at Neutral because it pairs real Phase 2 human trials with a narrow, niche use and a stalled development path. It activates the innate repair receptor, the EPO receptor joined to the beta-common receptor (CD131), to calm overactive innate immunity and drive small-fiber nerve repair. The clever part is what it leaves out: it skips the EPO-receptor homodimer that raises red blood cells and clotting, so you get the protective signaling of EPO without its blood risk. The headline human result is structural, with a significant rise in corneal nerve fiber area at 4 mg per day, per Culver 2017. That is rare for a grey-market peptide, which is why it scores at the top of this repair group.
Here is the honest tradeoff. ARA-290 has a small but legitimate Phase 2 program in small-fiber neuropathy, in both sarcoidosis and diabetes, with trials usually under 100 patients. It never reached Phase 3, the developer Araim appears to have ceased operations, and human-use supply is research-chemical only. So this is the most evidence-backed peptide in its niche, resting on surrogate endpoints in small trials, for a problem most people do not have.
The single most citable number: 4 mg per day raised corneal nerve fiber area by a placebo-corrected 697 square micrometers, while 8 mg lost significance. More is not better here, an inverted-U.Culver 2017, Invest Ophthalmol Vis Sci
Terminology
A few terms decide how you read this report, because ARA-290's whole pitch lives in the difference between two erythropoietin receptors, and because the trial endpoints are surrogates, not the symptoms you feel. Get these straight and the score makes sense; miss them and the niche, surrogate-heavy evidence looks stronger or weaker than it is. The single most important distinction is the receptor split, since that is what lets ARA-290 keep the repair signal of erythropoietin while leaving behind its blood-raising job. The second is the gap between a corneal nerve scan, which is what the trials measured, and the burning pain a patient actually feels, which moved less reliably. Hold both in mind and the Neutral score reads as honest rather than harsh.
- EPO: Erythropoietin, the hormone best known for raising red blood cells. ARA-290 is derived from one region of it but is engineered to avoid that blood-raising job.
- Innate repair receptor (IRR): The EPO receptor complexed with the beta-common receptor (CD131). This is the tissue-protection and repair receptor ARA-290 targets, and it is separate from the receptor that makes red blood cells.
- CD131 (beta-common receptor): The partner protein that, joined to the EPO receptor, forms the innate repair receptor. Knock it out in animals and ARA-290 stops working, which proves the mechanism.
- Small-fiber neuropathy (SFN): Damage to the small nerve fibers that carry pain and temperature, causing burning pain and numbness. It is ARA-290's main trial indication.
- Corneal nerve fiber density and area: A surrogate measure of small nerve health, read with a corneal scan. ARA-290's strongest endpoint is regrowth here, not a hard clinical outcome.
- pHBSP: Pyroglutamate helix-B surface peptide, another name for ARA-290 or cibinetide.
- Inverted-U: A dose-response where the middle dose works best and a higher dose does worse. ARA-290 shows this, with 4 mg beating 8 mg.
How do you take ARA-290 (Cibinetide)?
Dosing & Protocols
Dosing information is summarized from published research and community reports. This is not a prescribing guide. Consult a healthcare provider before starting any protocol.
View 1 route and 4 protocols
Routes & Forms
| Route | Form | Clinical Range | Community Range |
|---|---|---|---|
| Subcutaneous injection | Lyophilized peptide reconstituted with bacteriostatic water (research-chemical material; no pharmacopeial identity or purity guarantee) | No approved clinical dose; trials used 1 to 8 mg per day, with 4 mg per day the optimal arm | 1 to 4 mg per day subcutaneous |
Protocols
Trial-optimal (sarcoidosis or diabetic small-fiber neuropathy) Clinical
- Dose
- 4 mg
- Frequency
- Once daily
- Duration
- 28 days
The statistically significant arm for corneal nerve fiber regrowth in the Phase 2b dose-ranging trial, and the dose used in the type-2-diabetes Phase 2. Investigational, not an approved dose.
Low-dose probe Clinical
- Dose
- 2 mg
- Frequency
- Single dose or 3 times weekly
- Duration
- Up to 4 weeks
Reflects the early sarcoidosis pilot (2 mg three times weekly intravenously) and the single 2 mg subcutaneous dose used in the antidepressant probe. Lower exposure, weaker nerve signal.
Extended course Clinical
- Dose
- 4 mg
- Frequency
- Once daily
- Duration
- 12 weeks
The longest human dosing window, from the diabetic macular edema study. No approved long-term regimen exists, and chronic-use safety in people is unknown.
High-dose (not recommended) Clinical
- Dose
- 8 mg
- Frequency
- Once daily
- Duration
- 28 days
Tested in the dose-ranging trial and it lost significance versus 4 mg, an inverted-U. More is not better; included for contrast only.
How this score is calculated →
What are the benefits of ARA-290 (Cibinetide)?
Upside contribution: 2.18
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Efficacy | 25% | 3.3 | 0.825 | |
| Breadth | 15% | 3.1 | 0.465 | |
| Evidence | 25% | 3.5 | 0.875 | |
| Speed | 10% | 3.0 | 0.300 | |
| Durability | 10% | 2.2 | 0.220 | |
| Bioindividuality | 15% | 3.3 | 0.495 | |
| Total | 3.180 |
Upside Rationale
The upside comes from one thing done well: ARA-290 has genuine human RCT evidence for regrowing small nerve fibers, which most grey-market peptides cannot claim. The strongest single result is a significant rise in corneal nerve fiber area at 4 mg per day in a 64-patient dose-ranging trial, per Culver 2017. Evidence quality is the standout dimension here, not because the trials are large but because they are real, registered, placebo-controlled, and reproducible across two diseases. The key boundary is scope: the benefit is concentrated in small-fiber neuropathy, the endpoints are surrogates, and durability is mostly untested. So the upside is credible and specific rather than broad.
Efficacy (3.3/5.0): The clearest efficacy signal is structural nerve regrowth at the trial-optimal dose. In the Phase 2b dose-ranging trial, 4 mg per day raised corneal nerve fiber area by a placebo-corrected 697 square micrometers (p=0.012), the only significant arm, while regenerating GAP-43-positive fibers also rose, per Culver 2017. An earlier subcutaneous trial increased corneal nerve fiber density and walking capacity, per Dahan 2013, and the type-2-diabetes Phase 2 improved neuropathic symptoms with nerve regrowth in the most-affected subgroup, per Brines 2015. Efficacy does not score higher because the strongest endpoint is a surrogate, pain relief is less consistent, trials are small, and a macular edema study was null on its main ocular outcomes.
Breadth of Benefits (3.1/5.0): Breadth is moderate because the ARA-290 mechanism is broad but the proven benefits are narrow. The innate repair receptor touches nerve repair, anti-inflammatory signaling, and wound healing in principle, and a diabetic wound model showed faster re-epithelialization and angiogenesis, per Bitto 2018. The class was built to keep this protective signaling broadly, per Sanchis-Gomar 2013. But in people, the demonstrated breadth narrows to small-fiber neuropathy across two diseases, and adjacent claims fall away: the macular edema endpoints were null and an antidepressant probe did not clearly land, per Cerit 2015. Breadth of mechanism is not breadth of proof, so this scores in the middle. The fair read is that ARA-290 is a specialist tool with one well-mapped lane, not a general-purpose repair peptide that quietly helps a dozen systems at once.
Evidence Quality (3.5/5.0): Evidence quality is the strongest dimension and the reason ARA-290 sits at the top of this group. There are multiple registered, placebo-controlled Phase 2 RCTs, including the sarcoidosis pilot, per Heij 2012, the subcutaneous corneal-regrowth trial, and the dose-ranging trial, per Culver 2017. The signal reproduces across both sarcoidosis and diabetes, and animal work confirms receptor dependence in CD131 knockouts, per Swartjes 2013. It does not score higher because the trials are small (n about 9 to 64), no Phase 3 was completed, and the diabetic-neuropathy development landscape lists cibinetide as not yet delivered.
Speed of Onset (3.0/5.0): Onset is measured in weeks, not hours, because the benefit is tissue repair rather than a quick pharmacologic effect. Trials assessed nerve-structure and symptom changes over a 28-day course, with corneal nerve fiber area rising significantly by day 28, per Culver 2017. The peptide itself clears fast, with a plasma half-life of about 2 minutes, per Collino 2015, so the speed you care about is biological regrowth, not drug exposure. A month is a reasonable read-out window for the nerve endpoint.
Durability (2.2/5.0): Durability is the weak point because human dosing windows were short and follow-up is thin. Trials ran 28 days to 12 weeks, with no long-term human follow-up. There is one carry-over hint: the diabetes Phase 2 included a 28-day off-drug window where HbA1c and lipid gains persisted, per Brines 2015. Because the peptide promotes actual nerve regrowth rather than masking symptoms, some durability is plausible, but the roughly 2-minute half-life means benefit very likely needs continued or repeat dosing. Treat durable remission from a finite course as unproven.
Bioindividuality Upside (3.3/5.0): Response is predictably concentrated in the most-affected, which is a real strength for targeting. In the diabetes Phase 2, nerve regrowth was significant specifically in the subgroup whose baseline corneal nerve fiber density was more than one standard deviation below normal, per Brines 2015. In the dose-ranging trial, the moderate-to-severe-pain subgroup showed the larger pain change, per Culver 2017. So the people with the worst small-fiber loss are the likeliest responders, while those with mild or no neuropathy have little to gain. That clear responder profile lifts this dimension above average.
What are the risks & downsides of ARA-290 (Cibinetide)?
Downside contribution: 1.52 (safety risks weighted extra)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Safety | 30% | 2.0 | 0.600 | |
| Side effects | 15% | 2.0 | 0.300 | |
| Cost | 5% | 3.0 | 0.150 | |
| Effort | 5% | 3.0 | 0.150 | |
| Opportunity | 5% | 2.8 | 0.140 | |
| Dependency | 15% | 2.5 | 0.375 | |
| Reversibility | 25% | 1.8 | 0.450 | |
| Total | 2.165 | |||
| Harm subtotal × 1.4 | 2.415 | |||
| Opportunity subtotal × 1.0 | 0.440 | |||
| Combined downside | 2.855 | |||
| Baseline offset (constant) | −1.340 | |||
| Effective downside penalty | 1.515 |
Downside Rationale
The downside is not about acute danger; it is about uncertainty, access, and opportunity cost. ARA-290's safety is clean by design, since it skips EPO's blood-raising receptor, and trial adverse events were mild and transient. What weighs the score down is that the compound is investigational with no Phase 3, the developer has stalled, supply is research-chemical only, and the indication is narrow enough that most people would be spending effort on a problem they do not have. The most exposed person is someone treating a non-neuropathy goal, who carries all the access and uncertainty risk for benefits the trials never tested.
Safety Risk (2.0/5.0): ARA-290's safety is low-risk and clean by design, which is the whole point of the molecule. Because it activates only the innate repair receptor and skips the EPO-receptor homodimer, it does not raise hematocrit or carry EPO's clotting and red-blood-cell concerns, per Collino 2015. Across the human program, investigators reported no meaningful hematocrit rise and no significant safety signals, and the 12-week course produced no anti-drug antibodies, per Lois 2020. There is no intrinsic fatal signal. The honest gaps are duration and provenance: no long-term human safety data beyond 12 weeks, and a theoretical caution in active cancer for any EPO-pathway-adjacent agent, unstudied in people. The low score reflects a favorable profile, not the absence of unknowns, and the real-world risk shifts from the peptide itself to the unregulated vial it comes in.
Side Effect Profile (2.0/5.0): ARA-290 side effects were mild and transient throughout the human program, mostly injection-site reactions and occasional headache, with no pattern of serious events. The favorable profile held across the sarcoidosis and diabetes trials and the 12-week macular edema course, per Brines 2015 and Lois 2020. The realistic side-effect risk for a real-world buyer comes less from the peptide and more from research-chemical sourcing, where purity and endotoxin variability can introduce reactions the trials never saw with pharmaceutical-grade material. In other words, the molecule is gentle; the supply chain is where the real exposure sits.
Financial Cost (3.0/5.0): ARA-290 cost is moderate and ongoing. Research-grade material is sold in milligram quantities, and a trial-style 4 mg per day course adds up quickly over a 28-day to 12-week window, plausibly a few hundred dollars per cycle depending on vendor and dose. It is not a cheap experiment given that you are paying for an investigational compound with no pharmaceutical accountability, the price reflects research-chemical markups rather than economies of scale, and any monitoring bloodwork or clinician oversight adds to the total spend.
Time/Effort Burden (3.0/5.0): Effort with ARA-290 is meaningful but not extreme. The peptide requires reconstitution with bacteriostatic water, daily subcutaneous injection, cold-chain storage, and site rotation over a multi-week course, which is a real daily logistics load compared with an oral supplement. The bigger practical burden is sourcing and verification: confirming you have genuine material with a certificate of analysis, since there is no approved product and the research-chemical market carries mislabeling and purity risk that the trial supply never had.
Opportunity Cost (2.8/5.0): Opportunity cost is real and depends entirely on who you are. For refractory small-fiber neuropathy where standard options are poor, ARA-290 is arguably the best-evidenced peptide to discuss with a clinician, so opportunity cost is low. For general recovery, anti-inflammatory, or longevity goals, the cost is higher: the indication is narrow, broad-benefit claims are unproven, and the same effort could go to better-validated repair peptides or the training, sleep, and nutrition basics that move those goals with far more certainty.
Dependency/Withdrawal (2.5/5.0): Dependency risk with ARA-290 is low. It is not a hormone-axis suppressant the way exogenous growth hormone or testosterone can be, and there is no documented addiction or withdrawal syndrome in the trial record; benefits simply fade if the underlying repair is incomplete and dosing stops. The open question is not dependence but durability, since the roughly 2-minute half-life and 28-day-to-12-week trials mean continued or repeat dosing is likely needed to maintain symptom control. That is functional reliance on an ongoing effect, not a withdrawal problem, and stopping carries no rebound penalty in the published data.
Reversibility (1.8/5.0): Reversibility is excellent and clean. With a plasma half-life of about 2 minutes, per Collino 2015, the drug clears the system almost immediately, so stopping is straightforward and there is no taper or lingering exposure. The nerve regrowth it promotes is a beneficial structural change rather than a harmful permanent one, so a clean stop carries no known lasting downside. This near-instant clearance is one of the compound's genuine strengths and a sharp contrast with longer-acting peptides.
Is ARA-290 (Cibinetide) worth it?
ARA-290 sits at Neutral because it is the strongest peptide in this repair group on human-trial rigor, yet it is hemmed in by a narrow indication, small trials, no Phase 3, a defunct sponsor, and grey-market-only supply. The practical verdict splits by who you are. If you have refractory small-fiber neuropathy, especially sarcoidosis-associated or diabetic, this is the most evidence-backed peptide for that specific problem, with significant corneal nerve fiber regrowth at 4 mg per day, per Culver 2017, and a clean safety rationale. If you are stacking for general recovery or longevity, the score is generous: the proven benefit is narrow, broad claims are unproven, and you would be sourcing an investigational drug with no long-term human safety data. The Neutral tier is the honest middle: real human RCTs pull it up, while the niche scope, small trial sizes, stalled development, and grey-market supply pull it back down to a wash.
The design thesis is the safety story: because the protective and blood-raising effects of erythropoietin run through different receptors, a peptide aimed only at the repair receptor keeps the tissue protection and drops the clotting and red-blood-cell risk.Collino 2015, Pharmacol Ther
✅ Best for: People with refractory small-fiber neuropathy who have exhausted standard options and want the best-evidenced peptide for that niche. People with sarcoidosis-associated or diabetic neuropathic pain, the exact populations the trials studied, per Heij 2012. Those with the most severe small-fiber loss, who were the clearest responders in the diabetes Phase 2, per Brines 2015. Research-minded users who can work with a clinician, run baseline and follow-up monitoring, and verify material with a certificate of analysis. People who value a clean, non-erythropoietic safety rationale and a fully reversible profile.
❌ Avoid if: You have active or suspected cancer, since EPO-pathway-adjacent, tissue-growth-promoting agents are an unstudied risk in people. You are pregnant, breastfeeding, or considering it for a child, where no human safety data exists, per van Velzen 2014. You want general recovery, anti-inflammatory, or longevity benefits, which the human trials never demonstrated and a macular edema study failed to support, per Lois 2020. You cannot source verified, certificate-backed material, since the research-chemical market carries real purity and mislabeling risk. You want a proven, approved option, which this is not.
What is ARA-290 (Cibinetide) best for?
The overall BioHarmony score reflects the intervention's primary evidence profile. These subratings are independent assessments per use case.
Nerve Regeneration: 5.0/10
Score: 5.0/10Nerve regeneration is ARA-290's strongest case and the reason it scores at the top of this group. In the Phase 2b dose-ranging trial, 4 mg per day raised corneal nerve fiber area by a placebo-corrected 697 square micrometers, the only significant arm, per Culver 2017. Regenerating GAP-43-positive fibers also rose at 4 mg, and the structural change tracked with walking capacity. An earlier subcutaneous trial showed increased corneal small-nerve-fiber density, per Dahan 2013. Animal work confirms the effect runs through the innate repair receptor, since it vanishes in CD131 knockouts, per Swartjes 2013. The cap: these are surrogate endpoints in small trials, not hard outcomes.
| Use Case | Score | Summary |
|---|---|---|
| ○ Chronic Pain Management Primary | 4.5 | Chronic neuropathic pain has real but weaker support than the nerve-structure signal. The sarcoidosis pilot improved the Small Fiber Neuropathy Screening List score significantly versus placebo, per Heij 2012, and the type-2-diabetes Phase 2 improved the PainDetect neuropathic-symptom score, per Brines 2015. But in the dose-ranging trial, pain dropped in the moderate-to-severe subgroup without reaching significance, per Culver 2017. A secondary mechanism, blocking the TRPV1 nociceptor channel, adds biological plausibility, per Zhang 2016. Honest read: pain relief is plausible and partly shown, but less consistent than the regrowth data. |
| ○ Anti-Inflammatory Primary | 4.5 | Anti-inflammatory action is the core mechanism, well supported preclinically but thin on direct human inflammation endpoints. Activating the innate repair receptor dampens innate immune-cell activation and reprograms a tissue-damaging environment into a healing one, per Dahan 2016. A diabetic wound model showed it raised repair signals like VEGF and phospho-Akt and lowered oxidative markers, per Bitto 2018. The whole non-hematopoietic EPO-agonist class was built to keep this protective signaling while skipping red-blood-cell effects, per Sanchis-Gomar 2013. The boundary: human trials measured nerve and symptom endpoints, not direct inflammatory readouts, so the anti-inflammatory benefit in people is inferred more than measured. |
Frequently Asked Questions
What is ARA-290, and how does it work without EPO's blood effects?
ARA-290 (cibinetide) is an 11-amino-acid peptide modeled on the helix-B region of erythropoietin that activates the innate repair receptor, the EPO receptor joined to the beta-common receptor (CD131), per Dahan 2016. That receptor drives tissue repair and calms innate immune activation. Crucially, it skips the EPO-receptor homodimer that raises red blood cells and clotting, which is why the non-hematopoietic class was built this way, per Sanchis-Gomar 2013. So you get EPO's protective signaling without its blood risk.
How much ARA-290 was used in trials, and how is it dosed?
The trial-validated dose is 4 mg per day subcutaneous, the arm with the strongest evidence, per Culver 2017. It also was the dose in the type-2-diabetes Phase 2, per Brines 2015. Higher is not better: 8 mg lost significance, an inverted-U. Trials ran 28 days, with the longest at 12 weeks. There is no approved label, no titration guidance, and no validated long-term regimen, so any non-trial use is investigational.
What does the small-fiber-neuropathy evidence on ARA-290 actually show?
The reproducible signal is small-fiber-neuropathy structure and symptoms. In the dose-ranging trial, 4 mg per day significantly raised corneal nerve fiber area and regenerating fibers, per Culver 2017. An earlier subcutaneous trial increased corneal nerve fiber density, per Dahan 2013, and the diabetes Phase 2 improved neuropathic symptoms, per Brines 2015. The catch: trials were small, the strongest endpoint is a surrogate, and there is no Phase 3.
Who is ARA-290 actually for?
ARA-290 is for people with refractory small-fiber neuropathy, including sarcoidosis-associated and diabetic nerve pain, where it is the most evidence-backed peptide for that narrow problem, per Heij 2012. It is a poor fit for general recovery or longevity stacking: the diabetic macular edema study was null on its main endpoints, per Lois 2020, and broad-benefit claims are unproven. The indication is genuinely niche.
Is ARA-290 safe?
Trial safety was favorable and clean by design. Across the human program, investigators reported no meaningful hematocrit rise and only mild, transient events like injection-site reactions, per Brines 2015 and the 12-week course that showed no anti-drug antibodies, per Lois 2020. The honest caveats: no long-term human safety data beyond 12 weeks, and that clean record came from pharmaceutical-grade material, not research-chemical vials of unknown purity.
Who should avoid ARA-290?
Anyone with active or suspected cancer should avoid ARA-290, since EPO-pathway-adjacent, tissue-growth-promoting agents are an unstudied risk in people, even though the peptide lacks EPO's proliferative homodimer signaling. Pregnancy, breastfeeding, and pediatric use are off the table because no human safety data exists, per van Velzen 2014. For a clotting history the mechanism is reassuring, with no hematocrit effect, but there is no long-term confirmation, so caution and clinician oversight apply.
How long does ARA-290 take to work, and does the benefit last?
Trials measured nerve-structure and symptom changes over 28 days, with the longest course at 12 weeks, per Culver 2017. Durability is mostly untested. The plasma half-life is only about 2 minutes, so any lasting effect is downstream tissue repair, not the drug persisting. The diabetes Phase 2 saw HbA1c and lipid gains hold across a 28-day off-drug window, per Brines 2015, a hint of carry-over, but most benefit likely needs continued dosing.
ARA-290 versus EPO and versus other repair peptides: how does it compare?
Versus EPO, ARA-290 keeps the tissue-protective signaling but drops the red-blood-cell and clotting effects, since those run through a separate receptor, per Collino 2015. Versus other repair peptides, it has the opposite profile from BPC-157 and TB-500: genuine Phase 2 human RCTs but a narrow indication and worse access. It clears KPV on human-trial rigor, since KPV's case is largely preclinical.
What could change ARA-290 (Cibinetide)'s score?
BioHarmony scores are living assessments. New research, regulatory changes, or personal context can shift the score up or down. These are the most likely scenarios that would change this intervention's rating.
The fastest path up is a completed Phase 3 confirming the nerve-regrowth benefit, and the fastest path down is a credible safety signal or a definitive null in a larger trial. Because the current score rests on small but real Phase 2 data, a larger positive trial would lift Efficacy and Evidence together and push ARA-290 into worth-trying, while a clean-up of the access and development picture, a revived sponsor or an approved product, would ease the opportunity and effort weights. The dimensions most likely to move first are Evidence and Efficacy on new trial data, and Opportunity and Cost on a change in regulatory or supply status. The asymmetry to watch is that ARA-290 has more room to rise than to fall, since its safety floor is already favorable and most of what is holding it back is missing data rather than a known problem.
| Scenario | Dimension shifts | New Score |
|---|---|---|
| A completed Phase 3 confirms small-fiber-neuropathy benefit | Efficacy 3.3 to 4.0, Evidence 3.5 to 4.2 | 6.3 / 10 👍 Worth trying |
| An approved product reaches market with a clear label | Opportunity 2.8 to 2.0, Cost 3.0 to 2.4, Effort 3.0 to 2.4 | 6.0 / 10 👍 Worth trying |
| A larger trial extends benefit to broader nerve or repair uses | Breadth 3.1 to 3.8, Efficacy 3.3 to 3.7 | 6.1 / 10 👍 Worth trying |
| Long-term human data confirms durable benefit and safety | Durability 2.2 to 3.2, Safety 2.0 to 1.8 | 6.1 / 10 👍 Worth trying |
| A larger trial returns a definitive null on nerve endpoints | Efficacy 3.3 to 2.0, Evidence 3.5 to 2.5 | 5.1 / 10 ⚖️ Neutral |
| A credible long-term safety signal emerges in humans | Safety 2.0 to 3.2, Evidence 3.5 to 3.0 | 5.0 / 10 ⚖️ Neutral |
Key Evidence Sources
- Heij 2012, Mol Med: sarcoidosis small-fiber-neuropathy pilot RCT (n=22) improved the Small Fiber Neuropathy Screening List score versus placebo at 4 weeks, with no safety concerns.. 2012 randomized, double-blind, placebo-controlled pilot RCT; first human efficacy signal
- Dahan 2013, Mol Med: 28 days of daily subcutaneous ARA-290 improved neuropathic symptoms and significantly increased corneal small-nerve-fiber density and 6-minute-walk capacity.. 2013 blinded placebo-controlled RCT; corneal nerve fiber density regrowth
- Culver 2017, Invest Ophthalmol Vis Sci: Phase 2b dose-ranging RCT (n=64) found 4 mg per day significantly raised corneal nerve fiber area (p=0.012) while 8 mg lost significance, an inverted-U.. 2017 multicenter dose-ranging Phase 2b trial; defines the 4 mg optimal dose
- Brines 2015, Mol Med: type-2-diabetes Phase 2 trial, 4 mg per day subcutaneous for 28 days, improved Pai Detect neuropathic symptoms and corneal nerve fiber density in the most-affected subgroup with no safety issues.. 2015 Phase 2 controlled clinical trial in diabetic neuropathy
- Lois 2020, J Clin Med: diabetic macular edema Phase 2 study (n=9), 4 mg per day for 12 weeks, was null on visual acuity and retinal thickness but safe with no anti-drug antibodies.. 2020 single-arm Phase 2; null efficacy on ocular endpoints, longest dosing window
- Cerit 2015, Eur Neuropsychopharmacol: antidepressant probe RCT (n=36 healthy), single 2 mg dose, did not clearly support an antidepressant-like profile and was well tolerated.. 2015 RCT; near-null mood probe, low-dose safety data point
- Collino 2015, Pharmacol Ther: review of the innate repair receptor mechanism, the EPO-receptor and beta-common-receptor complex, and the roughly 2-minute plasma half-life of pHBSP.. 2015 mechanism review; receptor biology and pharmacokinetics
- Dahan 2016, Pain Rep: review synthesizing the innate-repair-receptor-targeting human program for neuropathy, including the immune-calming, pro-repair downstream signaling.. 2016 review of the human neuropathy program and mechanism
- Swartjes 2013, PLoS One: ARA-290 produced long-lasting relief of allodynia in normal mice but not in beta-common-receptor (CD131) knockouts, confirming the effect is innate-repair-receptor dependent.. 2013 preclinical study; genetic confirmation of receptor dependence
- Zhang 2016, Peptides: ARA-290 inhibited the TRPV1 nociceptor channel and blunted capsaicin-induced mechanical hypersensitivity, a secondary peripheral pain mechanism.. 2016 preclinical study; secondary nociceptor mechanism
- Bitto 2018, BBA Mol Basis Dis: in a diabetic wound model, cibinetide acting through the EPO-receptor and beta-common-receptor complex raised VEGF and phospho-Akt and improved re-epithelialization and wound breaking strength.. 2018 preclinical wound-healing study; repair signaling
- Sanchis-Gomar 2013, Mol Med: review of the non-hematopoietic erythropoietin-receptor-agonist class developed to preserve tissue protection without erythropoietic activity.. 2013 class review; rationale for non-hematopoietic design
- van Velzen 2014, Expert Opin Investig Drugs: review of ARA-290 for sarcoidosis-related small-fiber neuropathy and its investigational development status.. 2014 investigational-drug review; development and safety context
- Rendell 2021, Expert Opin Investig Drugs: review of the diabetic-neuropathy drug-development landscape that lists cibinetide among mechanisms that have not crossed the development finish line.. 2021 landscape review; confirms stalled development status
What does the evidence say about ARA-290 (Cibinetide)?
Evidence on this intervention is summarized across three complementary streams: contemporary clinical research, pre-RCT-era pharmacology and observational use, and the traditional medical systems that documented it first. Convergence across streams signals higher confidence; divergence is surfaced honestly.
Modern Clinical Research
Confidence: Medium
Citations: Culver 2017, Brines 2015, Dahan 2013
What to Track If You Try This
These are the data points that matter most while running a 30-day Experiment with this intervention.
How to read this section
- Pre
- Test or score before starting the protocol. Anchors a baseline.
- During
- Track while running the protocol so you can see if anything is changing.
- Post
- Re-test after a full cycle to confirm the change held.
- Up
- The marker should rise. For most positive outcomes, that is a good sign.
- Down
- The marker should fall. For most positive outcomes, that is a good sign.
- Stable
- The marker should hold steady. Big swings in either direction are a yellow flag.
- Watch
- Direction depends on dose, timing, and your baseline. Pay close attention to the trend.
- N/A
- No expected direction. The entry is there to anchor a baseline reading.
- Primary
- The Pulse dimension most likely to shift. Track this first.
- Secondary
- Also relevant, but a smaller or less consistent shift. Track if Primary is unclear.
Bloodwork to Order
Open These Markers In Your Dashboard
- hs-CRP Pre | Expected Watch During | Expected Down
- HbA1c During | Expected Watch
- Cbc During | Expected Stable
Pulse Dimensions to Watch
- Body During | Expected Watch | Primary
- Energy During | Expected Up | Secondary
- Calm During | Expected Watch | Tertiary
Subjective Signals (Daily Voice Card)
- Nerve pain intensity and burning or stabbing quality Scale 1-5 | During | Expected Down
- Numbness, tingling, or restored sensation in affected areas Scale 1-5 | During | Expected Watch
- Injection-site redness or warmth Scale 1-5 | During | Expected Watch
Red Flags: Stop and Consult
- Any active or suspected cancer: do not use; tissue-growth-promoting agents in the EPO pathway are an unstudied risk in people.
- New or worsening allergic-type reaction at or beyond the injection site: stop and consult a clinician.
- Pregnancy, breastfeeding, or pediatric use: no human safety data exists, so avoid.
- Product of unknown provenance or no certificate of analysis: the clean trial safety record was achieved with pharmaceutical-grade material and does not transfer to research-chemical vials.
Other interventions for Nerve Regeneration
See all ratings →📊 How BioHarmony scoring works
BioHarmony translates a weighted expected-value calculation into a reader-facing 0–10 score. Tier bands: Skip 0–3.6, Caution 3.7–4.7, Neutral 4.8–5.7, Worth Trying 5.8–6.9, Strong Recommend 7.0–7.9, Top-tier 8.0+.
Harm-type downsides (safety risk, side effects, reversibility, dependency) carry a 1.4× precautionary multiplier. Harm weighs more than benefit. Opportunity-type downsides (financial cost, time/effort, opportunity cost) are subtracted at face value.
Use case subratings are independent assessments of how well the intervention addresses specific health goals. They are not components of the overall score. Each subrating reflects the scorer's judgment based on use-case-specific evidence, safety, and effect sizes.
Every dimension is evaluated on a 1–5 scale, and the baseline (1) is subtracted before weighting. A perfect intervention with zero downsides contributes zero penalty rather than a residual floor, so top-tier scores are actually reachable.
EV = Upside − Downside
EV = 2.180 − 1.515 = 0.665
Formula v0.5 maps EV = 0 to score 5.0. Above neutral, 1 EV point equals 1 score point. Below neutral, 1 EV point equals about 0.71 score points, so EV = −7 reaches 0.0 while EV = +5 reaches 10.0. Both sides use the full 5-point half-scale.
Score = 5 + (0.665 / 5) × 5 = 5.7 / 10
