November 1, 2007

DMD Exon Skipping Trial Opens in UK

A trial of a synthetic compound that coaxes muscle cells to ignore a genetic mutation (abnormality) in the gene for dystrophin, the protein needed but missing in Duchenne muscular dystrophy (DMD), has opened in London.

The trial, which will include up to nine boys with DMD, will test at least two and possibly three dosage levels of AVI-4658, an antisense oligonucleotide (AO) that tells cells to ignore mutations in and around a section of the dystrophin gene known as exon 51 and splice together the genetic instructions surrounding the abnormality.

The hoped-for result is production of a functional dystrophin protein molecule, although this phase 1 safety trial is not expected to have any clinical benefit for the participants.

AVI-4658 was developed by an international team of investigators that included MDA-supported Stephen Wilton at the University of Western Australia in Perth and Judith van Deutekom of Leiden University in the Netherlands, working in collaboration with AVI BioPharma of Portland, Ore.
 
The AO strategy has recently shown promise in a small trial of a similar compound that was conducted in the Netherlands. In that trial, four out of four boys with DMD began making what appeared to be nearly normal dystrophin in an injected leg muscle. (See “Progress Reports, Trial Results,” May 11, 2007.)

The British clinical trial is funded by the United Kingdom Department of Health. The trial investigators, coordinated by Francesco Muntoni and colleagues at Imperial College London, are mainly seeking trial participants who are U.K. residents.

“Ideally, we would like not to put excessive burden on families for a proof-of-concept study that will not be personally beneficial to participants,” Muntoni said. “We would rather recruit families from the U.K. because of the practicalities.”

For details about the trial, see Safety and Efficacy Study of Antisense Oligonucleotides in Duchenne Muscular Dystrophy.