251. Gene-Based Interferon-Beta Therapy for Experimental Autoimmune Encephalomyelitis

In contrast to serial injections of recombinant protein, prolonged systemic delivery of proteins derived through in vivo gene transfer may ultimately provide a favorable alternative for long-term therapy of chronic inflammatory diseases such as the predominant use of interferon-beta (IFN|[beta]|) in the treatment of multiple sclerosis (MS). In the current study we compared the therapeutic efficacies of electroporation (EP) mediated intramuscular IFN|[beta]| gene transfer with repeated alternate day injections of recombinant IFN|[beta]| after onset of experimental autoimmune encephalomyelitis (EAE), an animal model widely used in MS research. Here we show for the first time that a single EP-mediated intramuscular administration of 20 |[mu]|g of an IFN|[beta]| expressing plasmid provides a therapeutic effect in established EAE comparable to an eight week regimen of 10,000 IU rIFN|[beta]| injected every other day. The achieved therapeutic effects involved a significant inhibition of disease progression and a significant reduction of EAE relapses compared to untreated mice or null vector treated mice. Gene delivery was achieved using a proprietary EP technology that controls plasmid injection and electric field application, thereby ensuring effective and reproducible administration to each subject. Our results indicate the viability of a convenient and effective gene-based alternative for long-term IFN|[beta]| protein therapy in MS and other chronic inflammatory disorders.