Sarcoidosis-associated small-fibre neuropathy — Phase 2
Phase IIStudies report improvement of neuropathic symptoms and increased corneal nerve fibre density in ARA-290–treated patients.
— Dahan et al. 2013, Mol Med 19:334-345 (PMID 24136731)
Helix-B-derived EPO mimetic (tissue-protective peptide) Limited Human Data
ARA-290
Also Known As: Cibinetide, pHBSP, pyroglutamate helix-B surface peptide
ARA-290 (cibinetide, formerly pHBSP) is an 11-residue peptide that mimics the helix-B surface region of human erythropoietin (EPO). It binds the heteromeric innate-repair receptor (EPOR-β common-receptor complex) but does NOT activate the classical homodimeric EPOR and therefore does not stimulate erythropoiesis. Developed by Araim Pharmaceuticals (Anthony Cerami, Michael Brines). Limited human data — small Phase 2 studies in diabetic neuropathy and sarcoidosis-associated neuropathies. Research use only.
Identity & Chemistry
- Amino Acid Sequence
- pyroGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (11-mer linear peptide derived from the helix-B surface region of human erythropoietin; N-terminal pyroglutamate)
- Molecular Formula
- C₅₃H₈₈N₁₆O₁₉
- Molecular Weight
- 1257.36 g·mol⁻¹
- CAS Number
- 1208243-50-8
- PubChem CID
- 71754655
- IUPAC Name
- Not publicly disclosed in a single canonical form; see PubChem CID 71754655 for the structural representation
Mechanism of Action
Studies report that ARA-290 binds the heteromeric innate-repair receptor (EPOR / β common-receptor / CD131) and triggers anti-inflammatory and neurotrophic signalling without activating the classical EPOR homodimer (and therefore without driving erythropoiesis).
The mechanistic rationale is that the tissue-protective (non-erythropoietic) effects of EPO are mediated via a separate heteromeric receptor (EPOR-β common). ARA-290 is engineered to selectively engage this receptor.
Molecular Targets
- Innate-repair receptor (EPOR / β common-receptor / CD131 heterodimer)
Signaling Pathways
- STAT3 modulation, anti-apoptotic and anti-inflammatory cascades
- No erythropoiesis stimulation (no classical EPOR-homodimer effect)
Research Applications
Small Phase 2 studies in sarcoidosis-associated small-fibre neuropathy and diabetic neuropathy report symptom improvement; Phase 3 data are lacking.
Type 2 diabetes with neuropathy — Phase 2
Phase IIStudies report improved metabolic control and reduced neuropathic symptoms.
— Brines et al. 2014, Mol Med 20:658-666 (PMID 25387363)
Clinical Status
Regulatory Status
ARA-290 / cibinetide is NOT approved — by the FDA, EMA or any other regulator. Investigational compound (Araim Pharmaceuticals).
Highest Trial Phase
Phase 2
Sponsor
Araim Pharmaceuticals
Safety Profile
Observed in research settings
Limited human data. In published Phase 2 studies, ARA-290 was described as well tolerated, without erythropoiesis stimulation and without the thrombotic events classically associated with EPO therapy. Observed in research settings.
Adverse Events Reported in Studies
- Injection-site reactions (reported)
References
-
Brines M, Patel NSA, Villa P, Brines C, Mennini T, De Paola M, Erbayraktar Z, Erbayraktar S, Sepodes B, Thiemermann C, Ghezzi P, Yamin M, Hand CC, Xie QW, Coleman T, Cerami A Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin Proceedings of the National Academy of Sciences USA 2008;105(31):10925-10930. 2008 .
-
Dahan A, Dunne A, Swartjes M, Proto PL, Heij L, Vogels O, van Velzen M, Sarton E, Niesters M, Tannemaat MR, Cerami A, Brines M ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density Molecular Medicine 2013;19:334-345. 2013 .
-
Brines M, Dunne AN, van Velzen M, Proto PL, Ostenson CG, Kirk RI, Petropoulos IN, Javed S, Malik RA, Cerami A, Dahan A ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes Molecular Medicine 2014;20:658-666. 2014 .
Frequently Asked Questions
Does ARA-290 stimulate red-cell production like EPO?
No. ARA-290 is engineered to selectively bind the heteromeric innate-repair receptor rather than the classical EPOR homodimer that drives erythropoiesis. No erythropoiesis stimulation has been reported in published studies.
Is ARA-290 approved?
No. ARA-290 (cibinetide) is an investigational compound. Clinical data are limited to small Phase 2 studies.
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