Ara-290 (16 mg vial)

Protocol Overview

Concise summary of the regimen.

Dosing & Reconstitution

Frequency: once daily subcutaneously, preferably into rotating thigh sites. Despite a very short blood half-life, about 2 minutes IV and about 20 minutes sub-Q, the receptor acts as a switch: a single dose activates the repair program and the cell continues running it after the drug clears. That is why daily dosing across a defined course produces effects that persist for months after the last dose. The dose sweet spot is unusually clean, since 4 mg worked, 1 mg was too low, and 8 mg was no better, so more is not stronger. Ara-290 is injected in its own syringe rather than mixed with other peptides. At 10 mg/mL the 4 mg dose is 40 units (0.40 mL), which draws into a single 1 mL U-100 insulin syringe with no need to split the injection.

Results Timeline

Sequence described in the research record. Individual response varies.

• Weeks 1 to 2: symptom change is typically the first thing reported, with burning, tingling, or shooting pain easing before any structural measure moves.
• Weeks 1 to 4: most measurable improvement accrues across the standard course of 28 days, and an extension to 12 weeks is the studied ceiling.
• After the last dose: nerve regeneration is slow, and benefit may keep accruing once dosing stops because the receptor program keeps running.
• Nine months after the last dose: in the sarcoidosis trial, symptom benefit was still present and nerve fiber measures had continued to improve.
• Several months later: a repeat course is considered only if symptoms return.

Reconstitution Steps

1. Draw 1.6 mL bacteriostatic water with a sterile syringe; an isotonic, sodium chloride containing diluent reduces injection sting.
2. Inject slowly down the vial wall; avoid foaming.
3. Gently swirl until dissolved (do not shake).
4. Label with date and concentration; refrigerate at 2 to 8 °C, protected from light. At 10 mg/mL, 1 unit = 0.01 mL » 100 mcg on a U-100 insulin syringe, so 4 mg = 40 units (0.40 mL) and 2 mg = 20 units (0.20 mL).

Storage Instructions

Proper storage preserves peptide quality.

• Lyophilized: store at minus 20 °C in dry, dark conditions; minimize moisture exposure.
• Reconstituted: refrigerate at 2 to 8 °C; use promptly and avoid freeze-thaw cycles.

• Allow vials to reach room temperature before opening to reduce condensation uptake.
• Inspect before each use: the solution should be clear and colorless, and is discarded if discolored or precipitated.

Supplies Needed

The figures below are based on the standard course of 28 days at 4 mg per day, which is 28 mg per week, with the extended course of 12 weeks shown alongside.

Peptide Vials (Ara-290, 16 mg vial):

• At 4 mg per day a 16 mg vial covers 4 days, so the 28 day course totals 112 mg, which is 7 vials, and a 12 week course totals 336 mg, which is 21 vials.

Insulin Syringes (U-100):

• Per week: 7 U-100 insulin syringes, one per day, since the 40 unit dose draws into a single 1 mL syringe.
• Full course: 28 syringes over 28 days, or 84 syringes over a 12 week course.

Bacteriostatic Water (10 mL bottles):

• Each 16 mg vial takes 1.6 mL, so one 10 mL bottle covers 6 vials, which is 2 bottles for the 7 vial course of 28 days and 4 bottles for the 21 vial course of 12 weeks.

Alcohol Swabs:

• Per injection: 2 swabs, one for the vial stopper and one for the site, which is 14 per week.
• Full course: 56 swabs over 28 days, or 168 over 12 weeks, so one 100 count box covers the standard course and two cover the extended one.

Important Notes

Practical considerations for consistency and safety.

• 4 mg is the trial-anchored dose. The dose ranging data is unusually clear: 8 mg is no better than 4 mg and 1 mg sits below the useful range, so there is no reason to escalate past 4 mg.
• Defined courses, not indefinite use. A course runs 4 to 12 weeks, and a repeat is run only if symptoms return after several months. No multi-year human data exists.
• Effects outlast dosing. In the sarcoidosis trial, symptom benefit persisted at 9 months after the last dose and nerve fiber measures kept improving after dosing stopped, which is switch-like pharmacodynamics showing up in the clinic.
• This is for nerve pain, not mechanical pain. Good fit: burning, tingling, electric or shooting pain, touch sensitivity (allodynia), numbness in a nerve territory, and temperature or sweating changes. Poor fit: deep ache, soreness, joint pain, swelling, and weakness without sensory symptoms, all of which belong with BPC-157 and TB-500.
• Administration is subcutaneous into rotating thigh sites, with an isotonic, sodium chloride containing bacteriostatic water to reduce sting, and Ara-290 goes into its own syringe. Stacking partners named in the master are BPC-157 and TB-500 for mechanical and structural repair when nerve pain sits inside a larger injury, SS-31 for mitochondrial support during repair, and NAD+ for cellular energy, with Tesamorelin layered in after nerve pain resolves for GH-axis support.
• Regulatory Note: Ara-290 holds FDA Fast Track and Orphan Drug designation for sarcoidosis but never entered Phase 3, and the developer has been dormant since 2020. There is no approved product, so purity and identity are not guaranteed across research peptide suppliers. This is a compound that stalled commercially rather than one that failed scientifically, and it remains for research use only, not for human consumption.

How This Works

Ara-290 was engineered by mapping erythropoietin's three dimensional structure and identifying helix B as the surface that contacts the innate repair receptor, a heterodimer of the EPO receptor paired with CD131, rather than the EPO receptor pair in bone marrow that drives red blood cell production. The 11 amino acid peptide reproduces helix B and selectively activates the repair receptor. Critically, that receptor is largely absent in healthy tissue and upregulated by injury, inflammation, or metabolic stress, so the drug has something to act on only where tissue is already damaged, which is why it is a poor fit for healthy people. Receptor binding triggers JAK2/STAT and PI3K/Akt signaling with downregulation of NF-kB inflammatory transcription, supporting cell survival and resolution of inflammation. Receptor dependence has been demonstrated independently in three organ systems: in CD131-knockout mice the analgesic effect in nerve injury disappeared, in stroke models neuroprotection was abolished, and in colitis models the anti-inflammatory effect required CD131. The short half-life, about 2 minutes IV and about 20 minutes sub-Q, combined with effects lasting days to months, reflects switch-like pharmacodynamics: the drug flips the receptor on and the cell continues running the repair program after the drug clears. In sarcoidosis trials, benefit was still measurable nine months after the last dose, and the 4 mg subcutaneous peak serum concentration of about 2 ng/mL sits just above the minimum effective receptor activating concentration.

Benefits & Side Effects

Observations from the published record.

• Sarcoidosis small fiber neuropathy is the strongest evidence, across three Phase 2 trials. In the DOSARA dose ranging trial (n=64), corneal nerve fiber area increased significantly at 4 mg and GAP-43 positive regenerating fibers rose 23% from baseline; Dahan 2013 (n=38) reported corneal nerve fiber area up 14.5% with symptom benefit sustained at 9 months; an earlier IV pilot (n=22) reported symptom score improvement of 11.5 versus 2.9 for placebo.
• Painful diabetic neuropathy: Brines 2015 (n=48 analyzed) found that 4 mg subcutaneous daily for 28 days improved PainDetect (p=0.037) and lowered HbA1c by 0.21% (p=0.002), with nerve fiber density improving in the subgroup that had baseline loss.
• Negative result honesty: the Lois 2020 diabetic macular edema trial (n=8, open-label) failed its primary vision endpoint, and the authors flagged that a fixed 4 mg dose may be too low for high body weight individuals. In DOSARA the between group pain difference did not reach significance (p=0.157) despite the nerve regeneration markers, so structural regeneration and symptom score signals were real while pain score signals were muddied by placebo effects.
• Hematology: hemoglobin was unchanged across all human trials, with no clinically significant changes in hematocrit or platelets and no anti-drug antibodies detected. That is the practical payoff of the non-erythropoietic design.
• Preclinical breadth: kidney ischemia-reperfusion protection, cardiac inflammation reduction in aged rats, a gut anti-inflammatory effect in colitis, brain protection in stroke models, and wound and bone healing, mostly rodent and cell data rather than human. Off-label post-surgical nerve pain, such as post-ACL saphenous nerve irritation, matches the mechanism from a rat surgical nerve injury study but has no human trial behind it.
• Side effects and safety limits: mild injection-site reactions, transient headache, and fatigue, at rates similar to placebo. Total human exposure remains small, at dozens of patients per trial and 12 weeks as the longest controlled course in 8 people, and the honest accounting includes one possibly related worsening of kidney function in the diabetic trial and one case of suicidal ideation in the 8 mg dose ranging arm.

Lifestyle Factors

Complementary strategies for best outcomes.

• Accurate identification of the pain type before starting. Ara-290 acts on nerve injury or inflammation, not on mechanical, joint, or load related pain, and the wrong target wastes the course.
• Physical therapy paired with the course where rehabilitation is part of recovery, since reduced nerve flares may allow better tolerance of PT.
• Glycemic control for diabetic neuropathy contexts: Ara-290 lowered HbA1c by 0.21% in the trial, but baseline metabolic control still drives outcomes.
• An anti-inflammatory baseline of omega-3 fatty acids, sleep, stress management, and avoidance of metabolic stressors supports the same resolution pathways Ara-290 activates.

Injection Technique

General subcutaneous guidance from clinical best-practice resources.

1. Clean the vial stopper and skin with alcohol; allow to dry.
2. Pinch a skinfold; insert the needle at 45 to 90 degrees into subcutaneous tissue.
3. Do not aspirate for subcutaneous injections; inject slowly and steadily.
4. Wait 5 to 10 seconds before withdrawing; dispose of syringe in sharps container.
5. Rotate sites systematically (abdomen, thighs, upper arms) to avoid lipohypertrophy.

References

Source citations for further reading.

1. Brines M et al. Nonerythropoietic, tissue-protective peptides derived from EPO; helix B surface peptide design (PNAS, 2008).
2. Swartjes M et al. ARA290 long-term relief of neuropathic pain; CD131 knockout abolishes effect (Anesthesiology, 2011).
3. Dahan A et al. 4 mg SC daily; CNFA +14.5%, 9-month sustained benefit (Mol Med, 2013).
4. Culver DA et al. DOSARA dose-ranging trial in sarcoidosis (Invest Ophthalmol Vis Sci, 2017).
5. Brines M et al. ARA 290 in painful diabetic neuropathy; HbA1c and PainDetect (Mol Med, 2015).
6. Lois N et al. ARA-290 in diabetic macular edema, negative primary endpoint (J Clin Med, 2020).