Exon Skipping Trial In DMD Slated for Spring

A pilot trial of antisense oligonucleotides (AONs) in older boys with Duchenne muscular dystrophy (DMD) is slated to open this spring in England in London and Newcastle Upon Tyne.

Nine boys, ages 14 to 18, will participate in the study, which will inject AONS into a foot muscle at three dosage levels. There will be three groups of three boys each at each level, and participants will be required to have certain types of genetic errors and be free of severe cardiac, respiratory or cognitive difficulties.

AONs are designed to cause exon skipping, a mechanism that coaxes cells to alter their processing of genetic instructions. In experiments in mice and in cells derived from DMD patients, production of the muscle protein dystrophin has been restored despite the presence of errors (mutations) in the dystrophin gene. Dystrophin mutations cause dystrophin deficiency, the root cause of DMD.

AONs, which can target a broader range of mutations than can compounds that cause cells to ignore premature stop codons, induce cells to leave out sections of genetic instructions that contain mistakes and join together the surrounding, correct instructions.

Stephen Wilton at the University of Western Australia in Perth and Qi Long Lu at Carolinas Medical Center in Charlotte, N.C., have MDA funding to develop exon skipping for DMD. Wilton says exon skipping clinical trials will likely begin in the United States and Australia if the British trial is encouraging.

For details on the British trial, go to www.clinicaltrials.gov, search for “antisense oligonucleotides,” and select the trial for Duchenne muscular dystrophy.