Prevention of Experimental Autoimmune Encephalomyelitis in Common Marmosets Using an Anti-IL-12p40 Monoclonal Antibody

Abstract

The experimental autoimmune encephalomyelitis (EAE) model in the common marmoset approximates recognized features of the human disease multiple sclerosis (MS) with regard to its clinical presentation as well as neuropathological and radiological aspects of the lesions in brain and spinal cord. IL-12 is a proinflammatory cytokine that is produced by APC and promotes differentiation of Th1 effector cells. IL-12 is produced in the developing lesions of patients with MS as well as in EAE-affected animals. Previously it was shown that interference in IL-12 pathways effectively prevents EAE in rodents. In this study we report that in vivo neutralization of IL-12p40 using a novel Ab has beneficial effects in the myelin-induced EAE model in common marmosets. The Ab was injected i.v. at 7-day intervals starting well after immunization (day 14) and was continued until the end of the study (day 86). Stable levels of the Ab were measured 3 days after each injection throughout the study period. During this period anti-Ab responses could not be detected. We demonstrate that anti-IL-12p40 treatment has a protective effect on the neurological dysfunction as well as on neuropathological changes normally observed in the brain and spinal cord of EAE-affected individuals.

Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis

“…Anti-IL-23p19 treatment effectively blocked both acute disease and EAE relapse, and histopathology showed absence of inflammatory cells in the spinal cord ( Figure 1 and Table 1). Consistent with previous reports, anti-p40 treatment was also remarkably effective (6,8,27). Isotype treatment groups showed 100% EAE incidence and severe inflammatory cell infiltration into the spinal cord.…”

Quantitative MRI‐pathology correlations of brain white matter lesions developing in a non‐human primate model of multiple sclerosis

“…This novel experimental model shows remarkable clinical and neuropathological similarity with MS (1,15). Therapies which have been beneficial in rodents are prophylactically (16,17) and therapeutically (6,7) confirmed in this model with MRI. However, it is unknown to what extent the histological changes occurring during lesions progression are reflected by MRI.…”

Gene therapy in nonhuman primate models of human autoimmune disease

“…66 Antibody-mediated neutralization of IL-12 had a strong protective effect on both the clinical and neuropathological expressions of EAE in marmosets. 67 Of special note in both studies was the observation that molecules with the size of an antibody could penetrate lesions and modify local immune responses.…”