ARA-290 (Cibinetide)

Structure: 11-amino-acid linear peptide (Gln-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser) derived from helix B of erythropoietin. INN: cibinetide.

Dosage (clinical trial range):

• Standard: 4mg SubQ, 3 times per week
• Sarcoidosis SFN trial dosing: 2 or 4mg SubQ daily for 28 days
• No grey-market consensus dose; clinical trial dosing is the most reliable starting point

Administration:

• SubQ injection, 27 to 30g insulin syringe
• Refrigerate after reconstitution

Key Notes:

• The TRT/PED-relevant angle: ARA-290 captures the tissue-protective effects of EPO (vascular endothelium, neurons, retinal cells, cardiac myocytes) WITHOUT raising haematocrit. For TRT users already managing borderline-high haematocrit, this is the differentiator from EPO.
• Anti-inflammatory mechanism is via the innate repair receptor, distinct from the classical EPO receptor on erythroid progenitor cells. This is why it does not stimulate red blood cell production.
• Strongest published clinical signal is in small-fibre neuropathy (sarcoidosis, type 2 diabetes), not in performance or recovery contexts.
• Anecdotal use in bodybuilding for nerve pain, post-surgical neuropathy, and recovery from peripheral nerve injury. Evidence base for these uses is limited to extrapolation from the SFN trials.
• Generally well tolerated in trials. Injection-site reactions are the most common adverse effect.
• Should NOT be expected to improve endurance, VO2 max, or oxygen-carrying capacity (those are EPO's haematopoietic effects, which ARA-290 lacks by design).
• Monitor: full blood count (to confirm haematocrit is NOT rising, useful as a quality-control check that the product is genuine ARA-290 and not contaminated with EPO), HbA1c if used long-term, symptom scales for the targeted neuropathy.

References:

• Brines, M., Patel, N. S., Villa, P., Brines, C., Mennini, T., De Paola, M., Erbayraktar, Z., Erbayraktar, S., Sepodes, B., Thiemermann, C., Ghezzi, P., Yamin, M., Hand, C. C., Xie, Q. W., Coleman, T., & Cerami, A. (2008). Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. PNAS, 105(31), 10925-10930. DOI: 10.1073/pnas.0805594105
• Dahan, A., Dunne, A., Swartjes, M., Proto, P. L., Heij, L., Vogels, O., van Velzen, M., Sarton, E., Niesters, M., Tannemaat, M. R., Cerami, A., & Brines, M. (2013). ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Molecular Medicine, 19(1), 334-345. DOI: 10.2119/molmed.2013.00146
• Heij, L., Niesters, M., Swartjes, M., Hoitsma, E., Drent, M., Dunne, A., Grutters, J. C., Vogels, O., Brines, M., Cerami, A., & Dahan, A. (2012). Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Molecular Medicine, 18(11), 1430-1436. DOI: 10.2119/molmed.2012.00332
• Brines, M., Dunne, A. N., van Velzen, M., Proto, P. L., Ostenson, C. G., Kirk, R. I., Petropoulos, I. N., Javed, S., Malik, R. A., Cerami, A., & Dahan, A. (2015). ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Molecular Medicine, 20(1), 658-666. DOI: 10.2119/molmed.2014.00215