Progress Reports, Trial Results
Presented at Conference

More than 40 speakers and some 150 registrants convened in Ottawa, Ontario, Canada, May 3-5 to celebrate the 20th anniversary of the identification of dystrophin, the protein that’s missing in boys with Duchenne muscular dystrophy (DMD) and deficient or abnormal in those with the milder variant Becker muscular dystrophy (BMD).

Nearly all presenters and many of the registrants are current or former MDA grantees, and many acknowledged MDA as the funding source that allowed them to start their careers. MDA, along with other organizations and companies, also contributed funding to the conference itself.

Among the presentations were updates on gene and cell transfer strategies; stop codon read-through, a strategy in which cells are coaxed to ignore abnormal stop signals in the dystrophin gene; stimulation of utrophin, a protein very similar to dystrophin that can at least partially compensate for its absence; and exon skipping, a technique in which error-containing sections of the dystrophin gene are masked, allowing production of functional dystrophin protein molecules. Exons are parts of genes that contain recipes (codes) for the final composition of a protein. Skipping exons changes the final protein content.

Gert van Ommen at Leiden (Netherlands) University presented what many consider the most exciting new data. He announced that four DMD-affected boys in the Netherlands who were given an exon skipping compound targeted to their genetic errors all began producing what appears to be functional dystrophin.

Van Ommen, with colleagues at Leiden University and at Prosensa, a Dutch biotech company, gave each of the 10 to 13-year-old boys a single injection of an exon skipping compound into a front lower leg muscle. All were missing sections of the dystrophin gene lying between exon 48 and exon 52.

MDA has supported Judith van Deutekom at Leiden University and Stephen Wilton at the University of Western Australia in Perth for development of exon skipping for several years. Skipping is accomplished with “antisense” compounds, which keep cells from obeying (making “sense” of) targeted genetic instructions.

Twenty-eight days after injection, biopsies of the boys showed strong and even dystrophin distribution in the injected area. There were no adverse effects except mild injection site pain.

The Dutch group is hoping to start systemic injections of this exon skipping antisense construct later this year.