Erythropoietin and Engineered Innate Repair Activators - Tissue-Protective Cytokines: Methods and Protocols - page 10

Fig. 4 The Innate Repair System. The endogenous tissue protective system is activated by inflammation caused
by tissue damage. In turn, inflammation induces an innate repair receptor immediately following injury, as well
as a delayed, less vigorous expression of hypoEPO. Activation of the innate repair receptor by an innate repair
activator damps further tissue damage and inflammation, as well as initiates multiple molecular pathways that
promote repair

In essence, this molecular switch functions as an innate repair
receptor (and its ligands-innate repair activators) that have been
shown to be composed of the

CR and EPOR, as well as other
receptor subunits relevant for specific tissues, e.g., VEGFR2 in
endothelial cells. Because the endogenous EPO system is activated
with a temporal delay and further, is also attenuated by
proinflammatory cytokines, the molecular switch that controls
inflammation and healing is an attractive target for therapeutics.
However, the presence of an additional receptor for EPO mediat-
ing hematopoiesis possessing an affinity significantly higher than
that for tissue protection and regeneration, makes renal EPO itself
a poor innate repair activator. Several different approaches have
produced engineered molecules that do not interact with the
hematopoietic-thrombotic system and therefore activate only tis-
sue protection and regeneration. This new class of therapeutics—
innate repair activators (IRAs)—targets the fundamental processes
of tissue injury at a level that controls both the self-damaging as
well as regenerative components. IRAs therefore offer much prom-
ise for beneficial therapeutic effects in a wide range of diseases and
injuries.

β

Disclosure of Interest

The authors are officers of Araim Pharmaceuticals and currently
hold stocks/shares in the company.