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

• Published in: Molecular therapy Vol. 13; no. S1; p. S96
• Main Authors: Jaini, Ritika, Hannaman, Drew, Johnson, Justin M., Bernard, Robert M., Altuntas, Cengiz Z., de las Alas, Maida M., Kesaraju, Pavani, Luxembourg, Alain, Evans, Claire F., Tuohy, Vincent K.
• Format: Journal Article
• Language: English
• Published: Milwaukee Elsevier Limited 01.05.2006
• Subjects: Encephalomyelitis; Gene therapy; Genomes; Huntingtons disease; Interferon; Neurodegeneration; Proteins; Radiation; Vectors (Biology); Luxembourg
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2006.08.278

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 (IFNβ) in the treatment of multiple sclerosis (MS). In the current study we compared the therapeutic efficacies of electroporation (EP) mediated intramuscular IFNβ gene transfer with repeated alternate day injections of recombinant IFNβ 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 μg of an IFNβ expressing plasmid provides a therapeutic effect in established EAE comparable to an eight week regimen of 10,000 IU rIFNβ 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 IFNβ protein therapy in MS and other chronic inflammatory disorders.