Side-by-side · Research reference
ARA 290vsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 2HUMAN-REVIEWED17/59 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
ARA 290
PE 22-28
Primary target
Innate repair receptor (EPO receptor / CD131 heterodimer)
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
EPO/CD131 → JAK2 activation → PI3K/AKT, MAPK signaling → anti-inflammatory, anti-apoptotic cascades
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Tissue protection, nerve fiber regeneration, suppression of inflammatory macrophage activation, altered T-cell differentiation (↑Treg, ↑Th2, ↓Th1)Liu 2014Culver 2017
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Feedback intact?
N/A — does not interact with hematopoietic EPO receptorLiu 2014
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
11-amino-acid sequence from EPO helix B, engineered to eliminate hematopoietic activity while retaining tissue-protective properties
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
Antibody development
Not reported in clinical trials
Not reported in animal studies
02Dosage Protocols
Parameter
ARA 290
PE 22-28
Standard dose (Phase 2)
4 mg / dayBrines 2015Culver 2017
Sarcoidosis SFN and diabetic neuropathy trials.
—
Frequency
Once daily
Self-administered subcutaneously.
Once daily
Sustained antidepressant effect over 7+ days.
Evidence basis
Phase 2 RCTsCulver 2017Brines 2015
64-subject sarcoidosis trial, type 2 diabetes trial.
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Timing
Any time of day
No circadian dependence reported.
—
Animal dose (antidepressant)
—
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
Animal dose (neuroprotection)
—
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
Onset (animal)
—
Within hours (acute); full effect 4–7 days
Comparison to fluoxetine
—
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
Human equivalent (extrapolated)
—
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
03Metabolic / Fat Loss Evidence
Parameter
ARA 290
PE 22-28
Primary effect
Improved metabolic control (HbA1c, fasting glucose)Brines 2015
Secondary to neuropathy treatment; direct lipolytic effects not established.
—
HbA1c
Significant reduction vs placebo
Observed in type 2 diabetes + neuropathy trial.
—
Fasting glucose
Improved in ARA 290 group
—
Body composition
Not directly quantified
Fat loss not a primary endpoint; metabolic improvements may reflect insulin sensitivity.
—
04Side Effects & Safety
Parameter
ARA 290
PE 22-28
Injection site reaction
Mild, transient
—
Hematopoiesis
None — non-erythropoietic
Distinguishes ARA 290 from native EPO.
—
Cardiovascular
No thrombotic events or hypertension reported
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Immunogenicity
No antibody formation reported
—
Toxicity (animal)
—
No adverse effects reported at therapeutic doses
Cardiovascular (theoretical)
—
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
Weight change
—
Not reported in animal studies
Neurological
—
No seizures or behavioral abnormalities noted
Long-term safety
—
Unknown — longest animal study 28 days
Absolute Contraindications
ARA 290
- ·Hypersensitivity to ARA 290
PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
ARA 290
- ·Active malignancy (theoretical EPO-axis concern; not observed in trials)
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
ARA 290
PE 22-28
1. Preparation
Reconstitute lyophilised powder per manufacturer instructions. Use sterile technique.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Injection site
Subcutaneous — abdomen, thigh, or upper arm. Rotate sites to avoid lipohypertrophy.
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Timing
Once daily, any time of day. Self-administered in Phase 2 trials.Brines 2015
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Dosing
4 mg daily for 28 days (Phase 2 protocol). Duration for chronic use not established.Culver 2017
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
5. Storage
Lyophilised: store at controlled room temperature. Reconstituted: refrigerate, use within specified timeframe.
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06Stack Synergy
ARA 290
+ BPC-157
ModerateARA 290 targets the innate repair receptor (EPO/CD131) for nerve regeneration and anti-inflammatory signaling, while BPC-157 promotes angiogenesis and tissue repair through distinct mechanisms (likely involving VEGF, growth hormone receptor pathways). Combined, they may address both neuroinflammation and structural tissue repair in neuropathy or injury models. No direct clinical data; mechanistic overlap in tissue protection.
- ARA 290
- 4 mg SQ · daily
- BPC-157
- 250–500 mcg SQ · daily
- Frequency
- Once daily, same or separate injections
- Primary benefit
- Nerve regeneration, pain reduction, tissue healing
PE 22-28
— no documented stacks