ARA290, a Peptide Derived from the Tertiary Structure of Erythropoietin, Produces Long-term Relief of Neuropathic Pain

Abstract

ARA290 produces long-term relief of allodynia because of activation of the β-common receptor. It is argued that relief of neuropathic pain attributable to ARA290 treatment is related to its antiinflammatory properties, possibly within the central nervous system. Because ARA290, in contrast to erythropoietin, is devoid of hematopoietic and cardiovascular side effects, ARA290 is a promising new drug in the prevention of peripheral nerve injury-induced neuropathic pain in humans.

The Receptor That Tames the Innate Immune Response

“…For example, in a mouse model of spinal cord injury, EPO is highly efficacious in restoring motor function after a 1-min cord compression, whereas mice in which βCR has been knocked out (35) are not protected. Similar effects were documented in vitro for cardiomyocytes (Figure 4B) and for neuropathic pain caused by sciatic nerve ligation (58). A biological role for βCR in tissue injury has been established by a number of other techniques than by gene KO to silence the βCR protein.…”

ARA 290 Improves Symptoms in Patients with Sarcoidosis-Associated Small Nerve Fiber Loss and Increases Corneal Nerve Fiber Density

“…The actions of ARA 290 are mediated through a receptor consisting of a complex formed by the erythropoietin receptor and β common receptor subunits (14), termed the innate repair receptor (IRR). In preclinical models of neuropathic pain, ARA 290 demonstrated beneficial effects that include IRR-dependent prevention of the development of allodynia in a peripheral nerve transection model (15) or in an inflammatory neuritis model (16), as well as attenuation of spinal cord inflammation (15). Also, erythropoietin, and its nonerythropoietic derivatives (for example, ARA 290) have been shown to support the regrowth of intraepidermal nerve fibers in preclinical models of neuropathy arising from toxins (17) or diabetes (18).…”

Delayed Administration of Pyroglutamate Helix B Surface Peptide (pHBSP), a Novel Nonerythropoietic Analog of Erythropoietin, Attenuates Acute Kidney Injury

“…These regions do not contain lysine and, therefore, are not modified by carbamylation of EPO, a procedure that produces a tissue-protective compound that is unable to bind to the classic EPO receptor (11). Subsequent studies have since identified that the novel tissue-protective peptide, pHBSP, can confer protection in a number of disease models (29)(30)(31)(32)(33)(34)(35)(36)(37). The interesting aspect of pHBSP is that it has many of the pleiotropic effects of EPO.…”