AVI BioPharma Publishes Preclinical Data in Muscular Dystrophy

Tag : Conjugate Fiber
Sustained Dystrophin Expression Found in Heart and Other Key Organs AVI BioPharma, Inc. (NASDAQ: AVII) todayannounced the publicationof preclinical results of a study designed todemonstrate theability of AVI's NeuGene® class of drugs to inducesustainedexpression of dystrophin in the mdx mouse model of Duchennemusculardystrophy (DMD). Treatment with the AVI compound resultedinproduction of functional dystrophin in numerous appropriatetissues,including the heart, diaphragm and skeletal muscles; keyorgans for thetreatment of the disease. The findings were publishedin the peer-reviewedjournal, Molecular Therapy.

http://www.nature.com/mt/journal/vaop/ncurrent/abs/mt2008120a.html

The paper, titled "Sustained Dystrophin Expression InducedbyPeptide-Conjugated Morpholino Oligomers in the Muscles of mdxMice," was acollaborative study by scientists from AVI, theUniversity of NorthCarolina at Chapel Hill and Mahidol University,Thailand.

In this study, a PMO-peptide conjugate, termed PPMO-B, that showedpotentactivity in skeletal muscles, diaphragm and, importantly, theheart wasinitially selected from a panel of other conjugates andsubsequentlyapplied for treatment of DMD in the mdx mouse model.The first finding ofthis investigation was that the systemicallydelivered PPMO-B induced highlevel of exon skipping in dystrophinmRNA in body-wide muscles, includingdiaphragm and cardiac muscle oftreated mice, without detectable toxicity.The induced dystrophinmRNA persisted for several weeks, indicating thatthe drug isretained and functional in the target organs for an extendedperiodof time. Furthermore, the mRNA effectively translatedsubstantialamounts of dystrophin protein in all target muscles.Dystrophin proteinpersisted in the muscles even longer than theRNA. Additional testsindicated improvement in muscle integrity and,specifically, reduction ofinflammation of the heart. This is thefirst report of PPMO-mediated exonskipping and functionaldystrophin protein induction in the heart oftreated animals.

"For DMD patients, restoration of functional dystrophin in heartanddiaphragm is critical because respiratory and cardiovascularcomplicationsare the ultimate cause of mortality," said Dr. RyszardKole, co-author andAVI's Senior Vice President of DiscoveryResearch. "This is the firststudy to establish peptide-conjugatedNeuGene drugs as potential treatmentfor DMD."

About Alternative RNA Splicing Technology

In normal genetic function, gene transcription produces afull-lengthpre-messenger RNA (pre-mRNA) that is then processed to amuch shorter andfunctional messenger RNA (mRNA). The mRNA is thetemplate for creating aprotein. During pre-mRNA processing, packetsof useful genetic information,called exons, are spliced together tomake the functional mRNA template,while unnecessary fragmentscalled introns are snipped out of thefull-length RNA. In somediseases, such as DMD, mutations derail thisprocess and preventproduction of functional dystrophin protein. AVI'sproprietarythird-generation NeuGene chemistry can be used to targetsplicingsites in the pre-mRNA, thus forcing the cell machinery to skipovertargeted exons, providing altered mRNA, which in turn producesalteredproteins. Skipping a defective exon can restore proper RNAreading frameand restore production of the protein to overcome thedevastating clinicalconsequences of the mutation.

About Duchenne Muscular Dystrophy

DMD is the most common fatal genetic disorder to affect childrenaround theworld. It is a devastating and incurable muscle-wastingdisease associatedwith specific inborn errors in the gene thatexpresses dystrophin, aprotein that is an essential component forstriated muscle function. Whendystrophin is missing ornonfunctional due to a mutation in the geneticcode of thedystrophin gene, as it is in DMD, the result is membraneleakage andfiber damage, ultimately leading to degeneration and death ofthemuscle fiber. Approximately one in 3,500 boys is born with DMD, andanestimated 15,000 to 20,000 children are afflicted in the UnitedStatesalone.

About AVI BioPharma

AVI BioPharma develops therapeutic products for the treatmentoflife-threatening diseases using third-generation NeuGene®antisense drugsand alternative RNA splicing technology. AVI'salternative RNA splicingtechnology is initially being applied topotential treatments for Duchennemuscular dystrophy. AVI's NeuGenecompounds are also designed to treatpost-operative cardiovascularrestenosis. In addition to targetingspecific genes in the body,AVI's antiviral program uses NeuGene antisensecompounds to combatdisease by targeting single-stranded RNA viruses,including MarburgMusoke and Ebola Zaire viruses. More information aboutAVI isavailable at www.avibio.com .

"Safe Harbor" Statement under the Private Securities LitigationReform Actof 1995: The statements that are not historical factscontained in thisrelease are forward-looking statements thatinvolve risks anduncertainties, including, but not limited to, theresults of research anddevelopment efforts, the results ofpreclinical and clinical testing, theeffect of regulation by theFDA and other agencies, the impact ofcompetitive products, productdevelopment, commercialization andtechnological difficulties, andother risks detailed in the company'sSecurities and ExchangeCommission filings.

AVI Press and Investor Contact:
Michael Hubbard
Director of Corporate Communications
Email Contact
(503) 227-0554