Gene-based intramuscular interferon-beta therapy for experimental autoimmune encephalomyelitis.
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.
Jaini
Ritika
R
Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Hannaman
Drew
D
Johnson
Justin M
JM
Bernard
Robert M
RM
Altuntas
Cengiz Z
CZ
Delasalas
Maida M
MM
Kesaraju
Pavani
P
Luxembourg
Alain
A
Evans
Claire F
CF
Tuohy
Vincent K
VK
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
D007370:Interferon Type I; D011994:Recombinant Proteins; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase