Beneficial effect of a multimerized immunoglobulin Fc in an animal model of inflammatory neuropathy (experimental autoimmune neuritis)

Abstract

Intravenous immunoglobulin (IVIg) is one of the first-line therapies for inflammatory neuropathies. Clinical use of IVIg for these disorders is limited by expense and availability. Here, we investigated a synthetic product alternative to IVIg. The aim of this study was to test the therapeutic efficacy of a novel recombinant polyvalent murine IgG2a Fc compound (stradomer™) in experimental autoimmune neuritis (EAN). Seventy-four Lewis rats were immunized with myelin, randomized into three groups, and were treated with albumin, IVIg, or stradomer at 1% of IVIg dose. Rats were assessed clinically, electrophysiologically, and histologically. The clinical disease severity was evaluated by clinical grading and weight changes. The electrophysiological studies recorded motor conduction velocity (MCV), amplitudes, and latencies of the evoked compound muscle action potential (CMAP) and spinal somatosensory evoked potential. The treatment efficacy of the IVIg and stradomer groups was compared to the albumin (control) group. We demonstrate that stradomer has a similar therapeutic efficacy to human IVIg in EAN. Rats receiving stradomer or IVIg showed significantly lower clinical scores and less prominent weight loss compared with controls. A statistically significant improvement in both MCV and the amplitudes of distal and proximal evoked CMAP was observed in the stradomer and IVIg groups. Finally, treatment with both IVIg and stradomer resulted in statistically less inflammation and demyelinating changes in the sciatic nerve as evidenced by lower histological grade. These results reveal the potential of using fully recombinant multimerized immunoglobulin Fc instead of IVIg for treating inflammatory neuropathies.

Recombinant IgG2a Fc (M045) multimers effectively suppress experimental autoimmune myasthenia gravis

“…Our findings in the IVIg-treated mice are consistent with an earlier study [33] which showed that IVIg can suppress disease in the rat model of EAMG. In addition, these results add to previously published studies in which fully recombinant IgG2a Fc multimers have been shown to alleviate collagen-induced arthritis in a dose-dependent fashion, to prevent idiopathic thrombocytopenic purpura in mice [25], and to ameliorate clinical, electrophysiologic, and histologic disease in experimental autoimmune neuritis (EAN) [34]. Interestingly, we noted a rapid decline in the clinical score shortly after each treatment with M045 and IVIG.…”

A recombinant human IgG1 Fc multimer designed to mimic the active fraction of IVIG in autoimmunity

“…M-045 avidly binds all murine Fcγ receptors (FcγRs) and mediates protection against platelet loss in a model of immune thrombocytopenic purpura (ITP), and therapeutic efficacy in a murine collagen-induced arthritis (CIA) model. Importantly, different scientific teams recapitulated the validity of these findings in models of myasthenia gravis and experimental autoimmune neuritis (27,28).…”

A fully recombinant human IgG1 Fc multimer (GL-2045) inhibits complement-mediated cytotoxicity and induces iC3b

“…The murine immunoglobulin G2a (IgG2a)-based version of this drug, M-045, was effective in the prevention and/ or treatment of a variety of rodent models of autoimmunity, including immune thrombocytopenic purpura, collagen-induced arthritis, 12 myasthenia gravis, 13 and experimental autoimmune neuritis. 14 Similarly, GL-2045 was effective in animal models of immune thrombocytopenic purpura and collagen-induced arthritis (X.Z. and J.O., manuscript submitted April 2016).…”