Recent

% | $
Quotes you view appear here for quick access.

Sarepta Therapeutics, Inc. Message Board

  • starfe11 starfe11 Sep 8, 2010 1:44 PM Flag

    “out-of-frame”

    AVI-4658, AVI BioPharma, Dr. Steve Shrewsbury
    Dr. Steve Shrewsbury, Chief Medical Officer for Seattle-based biotech AVI BioPharma, shared current progress on skipping exon 51 with AVI-4658, an antisense oligomer-based drug. The goal of this approach is to shift an “out-of-frame” deletion back into frame by “skipping over” some of the message (a single exon) used to make the protein—it’s somewhat analogous to trimming up a rough cut before pulling the edges together to patch something. The resulting protein is smaller than normal dystrophin but is expected to retain some function. Most of those with the milder Becker muscular dystrophy have in-frame rather than out-of-frame deletions. By skipping exon 51, AVI will attempt to bring back into frame a number of out-of-frame deletions that occur before and after this exon in the gene (such as deletions of exons 45-50, 47-50, 48-50, 49-50, 50, 52 and 52-63].

    SortNewest  |  Oldest  |  Most Replied Expand all replies
    • AVI-4658, AVI BioPharma, Dr. Steve Shrewsbury
      Dr. Steve Shrewsbury, Chief Medical Officer for Seattle-based biotech AVI BioPharma, shared current progress on skipping exon 51 with AVI-4658, an antisense oligomer-based drug. The goal of this approach is to shift an “out-of-frame” deletion back into frame by “skipping over” some of the message (a single exon) used to make the protein—it’s somewhat analogous to trimming up a rough cut before pulling the edges together to patch something. The resulting protein is smaller than normal dystrophin but is expected to retain some function. Most of those with the milder Becker muscular dystrophy have in-frame rather than out-of-frame deletions. By skipping exon 51, AVI will attempt to bring back into frame a number of out-of-frame deletions that occur before and after this exon in the gene (such as deletions of exons 45-50, 47-50, 48-50, 49-50, 50, 52 and 52-63].
      Dr. Shrewsbury first summarized the preliminary preclinical (animal) safety testing for AVI-4658, which showednoadversefindingsinavarietyofpharmacology,genotoxicityandtoxicitytests. Thenhe presentedinterimdatafromthephaseIB/2clinicalstudythatwasbegunonFebruary18,2009. The primary objective of this study was safety and tolerability. The study design included six groups of boys (cohorts) who received weekly infusions of AVI-4658 ranging from 0.5mg/kg to 20mg/kg for 12 weeks. At least one participant each in the 2mg/kg, 10mg/kg and 20mg/kg groups showed signs of substantial new dystrophin positive fiber expression over background by muscle biopsy at the end of the study. By the end of the study, two subjects who only had 1% dystrophin-positive muscle fibers before treatment had increases to 15% and 21%, respectively, and one individual who had 3% dystrophin-positive fibers increased to 55% at 20mg/kg. Two serious adverse events were reported but it was determined that neither was likely to be related to the study drug. The clinical data for this study will be available later this year and AVI currently is in preclinical development for compounds to skip exons 50, 44, 45 and 53.

 
SRPT
27.21-0.19(-0.69%)Aug 30 4:00 PMEDT