Synergistic Effects of IVIg and Erythropoietin (EPO) in Preclinical Models of Autoimmune Neuropathy (P01.154)

OBJECTIVE: To examine the potential antagonistic/synergistic effects of IVIg and EPO in preclinical models of anti-ganglioside antibody (Ab)-mediated neuropathy and inhibition of axon regeneration. BACKGROUND: Anti-ganglioside antibodies (Abs) are commonly present in patients with Guillain-Barre syndrome (GBS). We and others have shown that intravenous immunoglobulins (IVIg) can prevent anti-ganglioside Abs mediated complement dependent nerve cell/fiber injury. Our recent studies suggest that erythropoietin (EPO) enhances nerve repair in preclinical models of GBS. IVIg is now the standard treatment for GBS and a new trial to examine the efficacy of EPO in GBS would have to be done as add on therapy with IVIg. It is necessary to demonstrate that EPO and IVIg do not have antagonistic effects. It would also be important to know whether these two medications have synergistic effects to design an effective administration schedule in patients with GBS. DESIGN/METHODS: Previously published preclinical models of autoimmune neuropathy mediated by anti-ganlioside Ab were used to examine the potential antagonistic/synergistic effects of IVIg and EPO. RESULTS: Our results show that individual treatments with either IVIg or EPO provide significant protection, i.e., postpone the anti-ganglioside Ab- and complement-mediated neural injury to the neurites and neuronal cell body, in the neurocytotoxicity assays. Notably, no antagonistic effects were seen with the combined use of IVIg and EPO in these assays. Our data suggest that EPO and IVIg have synergistic effects in protecting neuronal cells from this anti-ganglioside Ab-mediated complement-dependent injury. CONCLUSIONS: Our results support the conclusion that EPO can be useful add-on therapy to the current standard IVIg treatment for GBS. This novel combination therapy can be potentially beneficial for protecting nerve from injury during the acute phase and enhancing nerve repair in the recovery period in GBS patients. Supported by: GBS/CIDP Foundation and NIH/NINDS (NS42888 and NS54962). Disclosure: Dr. Zhang has nothing to disclose. Dr. Bogdanova has nothing to disclose. Dr. Song has nothing to disclose. Dr. Sheikh has received royalty payments from Johns Hopkins University Licensing office.