Preclinical Assessment of EPO-Derived Peptide JM4 in Experimental Autoimmune Neuritis (P10-5.008)

Abstract

<h3>Objective:</h3> Determine clinical efficacy of JM4, a synthetic erythropoietin-derived 19-mer peptide in experimental autoimmune neuritis (EAN). <h3>Background:</h3> Guillain-Barré syndrome, an acute inflammatory demyelinating polyneuropathy (AIDP), is an autoimmune disease causing injuries to myelinated nerves. Mild AIDP cases result in temporary motor and sensory deficits, but severe AIDP cases can also cause dysautonomia and respiratory failure leading to disability or death. Treatments include intravenous immune globulin or plasma exchange, but only 30–40% of patients experience clinical improvement. More effective interventions are needed to improve AIDP clinical outcomes. JM4 is a 19-mer peptide derived from human erythropoietin, which does not have an unwanted side effect of erythropoiesis. We demonstrated JM4 therapy had prolonged therapeutic benefits in an experimental autoimmune encephalomyelitis (EAE) model. Since inflammatory mechanisms underlying EAE are shared with EAN, an animal model for AIDP, we reasoned JM4 would also have clinical benefit in EAN. <h3>Design/Methods:</h3> EAN was induced in C57BL/6 mouse and in Lewis rat using murine peripheral nerve myelin P0 antigen and bovine myelin P2 peptide, respectively. EAN clinical scoring paradigm was used to assess neurological deficits. At deficit onset, EAN mice were administered JM4 intravenously (IV) for 10 days and EAN rats were administered JM4 IV for 3 days followed by intraperitoneal injection for 7 days. Sciatic nerves from EAN rodents were stained with Luxol fast blue to assess demyelination and with cresyl violet to assess mononuclear cell infiltration. <h3>Results:</h3> JM4 treatment reduced peak EAN clinical scores compared to sham treatment. Based on staining analysis, EAN induction caused mononuclear cell infiltration and demyelination in the sciatic nerve. <h3>Conclusions:</h3> Preliminary clinical scoring data from rodent models suggest JM4 may have therapeutic benefits in EAN models. Further studies are needed to correlate improvements in clinical scoring with histological analysis of demyelination, mononuclear cell infiltration and neuroinflammatory markers in EAN models. <b>Disclosure:</b> Dr. Arismendi has nothing to disclose. The institution of Dr. Choi has received research support from Department of Veterans Affairs. Dr. Husar has nothing to disclose. Peter C. Dowling, MD has nothing to disclose. Dr. Lu has nothing to disclose.