Another preclinical treatment. This one sounds a bit different.
Successful Muscular Dystrophy Treatment Results Using AVI BioPharma Technology Published in Nature Medicine
BUSINESS WIRE - Feb. 9, 2006 - AVI BioPharma today announced that successful results from a new application of its proprietary NEUGENE(R) antisense technology, called ESPRIT (Exon Skipping Pre-RNA Interference Technology), were reported in the February issue of the prestigious scientific journal Nature Medicine by AVI collaborators at the Australian Neuromuscular Research Institute in Nedlands, Western Australia. The paper is titled "Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology," and relates to the treatment of Duchenne muscular dystrophy (DMD) in a mouse model of the disease.
ESPRIT therapeutics are designed to either delete disease-causing genetic sequences or skip functional sequences to redesign proteins that are overexpressed or harmful in certain diseases.
"This is a new approach to solving genetic disorders and diseases caused by overexpressed or harmful genes," said Denis R. Burger, Ph.D., chief executive officer of AVI. "ESPRIT therapeutics allow for fine genetic surgery at the RNA processing level, providing a new and very potent tool for altering many disease mechanisms. In addition to genetic disorders such as muscular dystrophy, AVI is now applying the ESPRIT therapeutic approach to diseases with an immunologic component, such as diabetes and multiple sclerosis."
In normal genetic function, gene transcription produces a full-length pre-RNA that is then processed to a much shorter and functional messenger RNA. The mRNA is the template for creating a protein. During pre-RNA processing, packets of useful genetic information, called exons, are snipped out of the full-length RNA and spliced together to make the functional mRNA template. AVI's proprietary third-generation NEUGENE chemistry can be used to target splice-joining sites in the pre-RNA, thus forcing the cell machinery to skip over targeted exons, providing altered mRNA, which in turn produces altered proteins.
Targeting the defective DMD dystrophin pre-RNA with an ESPRIT compound, Dr. Steve Wilton, associate professor and head of the Experimental Molecular Medicine Group at the Australian Neuromuscular Research Institute, forced the cell to snip out the disease-causing mutation region. Using this approach, a functional, but altered, dystrophin protein was made from a DMD gene that would previously have only made a nonfunctional protein.
"Antisense oligomers can alter gene expression by snipping out the disease-causing mutation of a gene transcript during the splicing step of gene expression to convert DMD to the much less disabling Becker muscular dystrophy," said Dr. Wilton. "Morpholino antisense oligomers appear to be the most efficient chemistry approach for exon-skipping, as they exhibit low toxicity, have been administered systemically, results persist for months in the body, and several compounds have already been used in human clinical trials."