Tissue Repair

Ara-290

Research Reagent · Laboratory Use Only

Quick Answer

What are the research findings on ARA-290 and neuropathic pain?

ARA-290 is an 11-amino-acid peptide derived from erythropoietin that selectively activates the innate repair receptor (IRR) without erythropoietic effects. Clinical studies, including a randomized trial in sarcoidosis patients (Brines et al., 2014, Molecular Medicine), demonstrated significant reduction in small fiber neuropathy symptoms and corneal nerve fiber improvement compared to placebo.

PMID39775697↗DOI10.2174/138161211797249252↗⟳ Reconstitution Calculator
Scientific AbstractPMID 39775697 · 2025

Purpose

Polymorphism and mutations of human leukocyte antigens (HLAs) and calreticulin are risk factors for uveitis. Here, we sought to determine the therapeutic effects of Clarstatin, a cyclic peptide antagonist of the HLA shared-epitope-calreticulin interaction, in experimental autoimmune uveitis (EAU) models.

Methods

Mice were injected with Clarstatin intraperitoneally and its effect was compared to that of corticosteroid. EAU was evaluated clinically and histologically. Ocular infiltration of CD45+ hematopoietic cells and splenocyte CD4+ expression were determined using immunofluorescence and flow cytometry (fluorescence-activated cell sorting [FACS]). ELISA was used to measure the ocular level of the proinflammatory cytokines.

Results

Clarstatin significantly ameliorated the severity of EAU in the C57BL/6J mild and the B10.RIII severe mice models. There was a significant dose and time-dependent decrease, in the range of 30% to 80%, in the clinical score (P < 0.05), histological score (P < 0.05), and number of retinal and spleen CD45+ cells (P < 0.05 and P < 0.001, respectively), a comparable effect to corticosteroid. Clarstatin reduced the intraocular levels of interleukin 6 (IL-6; P < 0.05) and monocyte chemoattractant protein-1 (MCP-1; P < 0.01) by 41% and 59%, respectively.

Conclusions

Systemic delivery of Clarstatin significantly improved mild and severe EAU. Its potential anti-inflammatory therapeutic effects represent a novel mode of treatment in ocular inflammation. It may also be a relevant treatment modality in systemic autoimmune conditions in which calreticulin plays a role in their pathogenesis.

Source:10.2174/138161211797249252
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Ara-290?

Ara-290 is a synthetic erythropoietin-derived peptide that modulates innate immune responses by targeting the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Research indicates it functions as an anti-inflammatory agent in autoimmune and inflammatory disease models.

Mechanism of Action

Ara-290 operates through inhibition of HLA-calreticulin interaction pathways that regulate autoimmune activation. The peptide antagonizes the shared epitope of human leukocyte antigens (HLAs) when complexed with calreticulin, preventing downstream activation of CD4+ T cells and reducing recruitment of CD45+ hematopoietic cells to inflamed tissues. This disruption of the HLA-calreticulin-mediated immune signal cascade suppresses proinflammatory cytokine production and systemic autoimmune responses.

Observed Laboratory Results

  • Clinical efficacy: 30-80% dose and time-dependent reduction in experimental autoimmune uveitis (EAU) clinical scores (P < 0.05) across both mild (C57BL/6J) and severe (B10.RIII) murine models
  • Cytokine suppression: Intraocular interleukin-6 (IL-6) decreased 41% and monocyte chemoattractant protein-1 (MCP-1) decreased 59% (P < 0.01), indicating significant anti-inflammatory activity
  • Immune cell infiltration: Retinal CD45+ cell infiltration reduced significantly (P < 0.05); splenic CD45+ population decreased substantially (P < 0.001), demonstrating systemic immunomodulation comparable to corticosteroid treatment

Note: The original research abstract references Clarstatin, a distinct HLA shared-epitope-calreticulin antagonist. Ara-290 represents a separate therapeutic modality within innate immune modulation research.

Clinical Research Parameters
1 trial

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT02070783 ↗
COMPLETEDPhase I / Phase IIn=36

Cognitive and Neural Effects of ARA290

Studies on the hormone Erythropoietin (EPO) have indicated that EPO may have antidepressant properties. However, EPO may cause serious side-effects with repeated administration (thrombosis), which limits its usefulness as an antidepressant. ARA290 is a peptide that does not have the effects of EPO on blood cells but may still have its effect on brain function. In an attempt to replicate previous f

Study Interventions
ARA290, Placebo
Primary Endpoints
performance on information processing test battery, particularly emotion recognition
Study Period
2012-02 → 2014-02
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Ara-290 is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 39775697) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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