AVI BioPharma Publishes Preclinical Data Reducing Inflammation in Hepatitis and Arthritis
May 12 2008 - 1:46PM
Marketwired
PORTLAND, OR today announced the publication of preclinical
results of a study designed to reduce the severity of disease in
mouse models of TNF-alpha induced hepatitis and collagen-induced
arthritis. The paper appears in the peer-reviewed journal,
Molecular Therapy.
(http://www.nature.com/mt/journal/vaop/ncurrent/index.html).
The publication titled, "An Endogenous TNF-alpha Antagonist
Induced by Splice Switching Oligonucleotides Reduces Inflammation
in Hepatitis and Arthritis in Mouse Models," was a collaborative
study by scientists from Ercole Biotech, Inc., which was acquired
by AVI in March 2008, University of North Carolina, Chapel Hill,
NC, and Santaris Pharma, Horsholm, Denmark.
TNF-alpha is a key mediator of inflammatory diseases, including
rheumatoid arthritis (RA). Splice switching oligonucleotides, are a
new class of drugs used to modify alternative RNA splicing in order
to induce therapeutically favorable splice variants of targeted
genes. In this study, treatment with LNA oligonucleotides,
developed by Santaris, induced alternative RNA splicing of TNF
receptor 2, resulting in a switch from the membrane-bound to a
soluble protein form, thus creating a "decoy" receptor, which
accumulated in the circulation of treated mice. The generated
soluble TNF receptor protein antagonized TNF-alpha, interfered with
its inflammatory function, and reduced severity of inflammatory
disease in mouse models of hepatitis and arthritis. This is the
first report of upregulation of the endogenous, circulating
TNF-alpha antagonist by oligonucleotide-induced modulation of
splicing.
"If our preclinical results can be replicated in the clinic,
this would represent a novel therapeutic approach and should also
be applicable to other indications. The oligonucleotide creates an
anti-inflammatory protein in situ in the treated animal, which we
hope will also happen in patients, and it persists in the
circulation for weeks," said Dr. Ryszard Kole, co-author of the
study and AVI's Senior Vice President of Discovery Research. "The
market for inflammatory diseases, including rheumatoid arthritis,
is huge. Moreover, this approach is not limited to a single
receptor. It should be also applicable to other indications."
About Inflammatory Disease and Rheumatoid Arthritis
TNF-mediated inflammatory diseases include a group of autoimmune
disorders such as Crohn's disease, ulcerative colitis, systemic
lupus erythematosus, rheumatoid arthritis, and multiple sclerosis.
Autoimmune diseases are illnesses that occur when the body tissues
are mistakenly attacked by one's own immune system.
Rheumatoid arthritis (RA) is a TNF-mediated chronic disorder
that leads to inflammation of the joints as well as other organs of
the body. Severe RA is a disabling condition, which leads to
substantial loss of mobility due to pain and joint destruction.
The National Institutes of Health estimates that approximately 2
million people in the United States suffer from rheumatoid
arthritis, occurring in all races and ethnic groups, with a
financial impact in the billions of dollars annually.
Anti-TNF biologics are the newest class of anti-inflammatory and
anti-rheumatoid arthritis drugs.
About AVI BioPharma
AVI BioPharma develops therapeutic products for the treatment of
life-threatening diseases using third-generation NeuGene� antisense
drugs and ESPRIT, directed RNA alternative splicing technology.
AVI's ESPRIT technology is initially being applied to potential
treatments for Duchenne muscular dystrophy. AVI's NeuGene compounds
are also designed to treat cardiovascular restenosis in stent and
coronary artery bypass graft (CABG) procedures. In addition to
targeting specific genes in the body, AVI's antiviral program uses
NeuGene antisense compounds to combat disease by targeting
single-stranded RNA viruses, including Marburg Musoke and Ebola
Zaire viruses. More information about AVI is available at
www.avibio.com.
"Safe Harbor" Statement under the Private Securities Litigation
Reform Act of 1995: The statements that are not historical facts
contained in this release are forward-looking statements that
involve risks and uncertainties, including, but not limited to, the
results of research and development efforts, the results of
preclinical and clinical testing, the effect of regulation by the
FDA and other agencies, the impact of competitive products, product
development, commercialization and technological difficulties, and
other risks detailed in the company's Securities and Exchange
Commission filings.
AVI Press and Investor Contact: Michael Hubbard Email Contact
Director of Corporate Communications (503) 227-0554
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