title: Gene-based intramuscular interferon-beta therapy for experimental autoimmune encephalomyelitis.
abstract: In contrast to serial injections of recombinant interferon-beta (IFN-beta) 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-beta gene transfer with repeated alternate-day injections of recombinant IFN-beta 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 microg of an IFN-beta-expressing plasmid provides long-term expression of interferon-inducible genes and is therapeutic in ongoing established EAE. The achieved therapeutic effects of IFN-beta gene delivery were comparable to an 8-week regimen of 10,000 IU rIFN-beta 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-beta protein therapy in MS.
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Ritika
authors.initials: R
authors.lastname: Jaini
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.forename: Justin M
authors.initials: JM
authors.lastname: Johnson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bernard
authors.forename: Cengiz Z
authors.initials: CZ
authors.lastname: Altuntas
authors.forename: Maida M
authors.initials: MM
authors.lastname: Delasalas
authors.forename: Pavani
authors.initials: P
authors.lastname: Kesaraju
authors.forename: Alain
authors.initials: A
authors.lastname: Luxembourg
authors.forename: Claire F
authors.initials: CF
authors.lastname: Evans
authors.forename: Vincent K
authors.initials: VK
authors.lastname: Tuohy
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018274:Electroporation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007370:Interferon Type I / Q000008:administration & dosage; D016899:Interferon-beta / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000628:therapy*; D018482:Muscle, Skeletal; D011994:Recombinant Proteins; D013154:Spleen / Q000201:enzymology
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase