Trial of 'Exon Skipping' Under Way in DMD

The first trial to test a treatment strategy known as exon skipping in boys with Duchenne muscular dystrophy (DMD) is now under way at Leiden University Medical Center in the Netherlands, according to Gerard Platenburg, CEO of the Dutch biopharmaceutical company Prosensa (www.prosensa.nl), the trial’s sponsor.

Exon skipping, which has shown promise in rodent models of DMD, is a technique that encourages cells to skip over faulty genetic information and construct a nearly normal protein from the remaining, correct information. (The parts of genes that supply codes for a protein’s structure are called “exons.”)

The strategy is accomplished through compounds known as antisense oligonucleotides, or AONs, which stick to specifically targeted genetic sequences (exons) and prevent the cell from using those exons when manufacturing a protein.

“This technique is really a sort of molecular surgery that takes advantage of natural processes in the cell to produce a shorter, but still functional, dystrophin protein,” said Sharon Hesterlee, MDA’s vice president for Translational Research. “It’s an innovative approach in which we’ve been interested for some time.”

In boys with DMD, the gene for the muscle protein dystrophin can have a variety of abnormalities, at least some of which can probably be circumvented by exon skipping.

The trial, which is fully enrolled, will include four to six boys with DMD who are between 8 and 16 years old. Each participant will receive a single intramuscular injection of an experimental AON.

The test AON was developed by Prosensa and builds on scientific contributions from many sources, including Judith van Deutekom at Leiden University’s Department of Genetics, who developed this type of therapy in mice and was an MDA grantee between 2003 and 2006.

Platenburg notes that this trial is an “exploratory study on the efficacy, safety and tolerability” of AON treatment in DMD. The investigators will see whether such treatment can restore production of dystrophin, which would provide “proof of principle” evidence that would encourage them to deliver the AON to the whole body.

“We have all reasons to expect that this trial will prove the therapeutic potential of our technology and thus form the basis for a viable cure for this terrible disease,” Plantenburg said.