Gene-Based Intramuscular Interferon-β Therapy for Experimental Autoimmune Encephalomyelitis

Abstract

In contrast to serial injections of recombinant interferon-β (IFN-β) for long-term therapy of multiple sclerosis (MS), prolonged systemic delivery of proteins derived through in vivo gene transfer may provide a more clinically relevant alternative. Here we compare the therapeutic efficacies of electroporation (EP)-mediated intramuscular IFN-β gene transfer with repeated alternate-day injections of recombinant IFN-β after the onset of relapsing–remitting experimental autoimmune encephalomyelitis (EAE), an animal model widely used in MS research. We show for the first time that a single EP-mediated intramuscular administration of 20 μg of an IFN-β-expressing plasmid provides long-term expression of interferon-inducible genes and is therapeutic in ongoing established EAE. The achieved therapeutic effects of IFN-β gene delivery were comparable to an 8-week regimen of 10,000 IU rIFN-β injected every other day and involved a significant inhibition of disease progression and a significant reduction of EAE relapses compared to untreated or null-vector-treated mice. Our results indicate the viability of a convenient and effective gene-based alternative for long-term IFN-β protein therapy in MS.