The EPICC
peptides are a family of
peptides that have been developed from the sequence of the
capsid protein of human astrovirus type 1 and previously shown to inhibit the classical and
lectin pathways of
complement. The EPICC
peptides have been further optimized to increase aqueous solubility and identify additional mechanisms of action. Our laboratory has developed the lead EPICC molecule,
PA-dPEG24 (also known as RLS-0071), which is composed of a 15
amino acid peptide with a C-terminal monodisperse 24-mer PEGylated moiety.
RLS-0071 has been demonstrated to possess other mechanisms of action in addition to
complement blockade that include the inhibition of neutrophil-driven
myeloperoxidase (MPO) activity, inhibition of neutrophil extracellular trap (NET) formation as well as intrinsic
antioxidant activity mediated by vicinal
cysteine residues contained within the
peptide sequence.
RLS-0071 has been tested in various ex vivo and in vivo systems and has shown promise for the treatment of both immune-mediated
hematological diseases where alterations in the classical complement pathway plays an important pathogenic role as well as in models of tissue-based diseases such as
acute lung injury and
hypoxic ischemic encephalopathy driven by both
complement and neutrophil-mediated pathways (i.e., MPO activity and NET formation). Next generation EPICC
peptides containing a
sarcosine residue substitution in various positions within the
peptide sequence possess aqueous solubility in the absence of PEGylation and demonstrate enhanced
complement and neutrophil inhibitory activity compared to
RLS-0071. This review details the development of the EPICC
peptides, elucidation of their dual-acting
complement and neutrophil inhibitory activities and efficacy in ex vivo systems using human clinical specimens and in vivo efficacy in
animal disease models.