ARA-290 & Nerve Repair Studies

ARA-290 is a peptide derived from the tertiary structure of Erythropoietin. It is under investigation for its neuroprotective properties.

Neuropathic pain is one of the most common manifestations in diabetic patients. The uncontrolled high sugar levels result in damage to the nerves. It interferes with their ability to send signals.

How Does ARA-290 Work?

ARA-290 peptide mainly works to reduce pain and improve the functioning of nerve fibers. These effects help fibers otherwise damaged due to small fiber neuropathy. Its mechanism of action is the activation of the β-common-receptor. The β-common-receptor plays a role in the non-hematopoietic effects mediated by Erythropoietin. The activated β-common-receptor combines with the EPO receptor to form a heterocomplex. This heterocomplex, also known as the Innate Repair Receptor or IRR, up-regulates locally in injured tissues. The IRR is an anti-inflammatory mediator whose activation inhibits the death signal, resulting in apoptosis. Due to its anti-inflammatory response, it prevents damage to the nervous tissues.

The IRR activation also promotes tissue repair responses and neurite growth in the nervous system. This two-way function of IRR makes the ARA-290 peptide a peptide that reduces tissue damage and promotes the healing of already injured tissue.

Potential Benefits of ARA-290

ARA-290 peptide is beneficial as an anti-inflammatory mediator and has been helpful in other conditions. Some of these are discussed below.

Diabetes
Studies on rats showed significant changes in blood glucose concentrations after administration of the ARA-290 peptide. After three or four weeks of ARA-290 peptide administration, the HbA1c levels were reduced by up to 20%. It was without changes in hepatic insulin sensitivity.

These changes in plasma glucose concentration were because the ARA-290 peptide improved β-cell metabolism. It also improves [Ca2+] handling and glucose-induced insulin release.

Non-Hematopoietic Erythropoietin–mediated Effects
Erythropoietin (EPO) is a cytokine that mainly plays a role in hematopoiesis (red cell production). It is also involved in anti-inflammatory, cytoprotective, and anti-apoptotic activities.

ARA-290 peptide, an EPO analog, has been studied, and experiments have proved that it exhibits cytoprotective and anti-inflammatory properties without the hematopoietic effects of EPO use.

Anti-Inflammatory effects on Kidneys
Trials conducted on animals showed that ARA-290 improved kidney function. The kidney functions were assessed by creatinine.

The improvement was noted mainly due to an increased glomerular filtration rate and reduced interstitial fibrosis due to a reduction in MCP-1 and IL-6 expression post-ARA-290 peptide administration. By phosphorylation of eNOS, it exhibited anti-inflammatory effects. This process leads to an overall improvement in renal function.

Regeneration of Injured Nerve Tissue
ARA-290 peptide, through its upregulation of the Innate Repair Receptor (IRR), activates two main pathways in nervous tissue that undergo diabetic neuropathy damage.

It initiates an anti-inflammatory response in the damaged tissues and, at the same time, promotes the healing and repair of the injured neurons.
This effect has been demonstrated in mice who suffered from mechanical and cold allodynia. This process lead to a decline in pain.

Protection against Hypoxia-induced Cellular Damage
In the case of limb ischemia, EPO undergoes upregulation. It opens the way for EPO analogs to protect against hypoxia-induced cellular damage and ischemia. Clinical trials on rats showed that the therapeutic administration of ARA-290 peptide reduced the concentrations of inflammatory cytokines.

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