And as for the "dystrophin as a surrogate" issue, here's some more from page 1 of the article:
"The challenge is that any effective therapy will need to restore dystrophin in both skeletal and heart muscle, and the treatment would need to be life-long. Studies of patients with X-linked dilated cardiomyopathy show that dystrophin levels as low as 30% in skeletal muscle are sufficient to prevent muscle weakness [REFERENCE GIVEN]. Nevertheless, delivery to all muscle, which constitutes ~35% of the body mass, is a considerable hurdle. Many therapies work well in the mdx mouse -- the frequently used animal model of the disease, which has a stop codon in exon 23 of the dystrophin gene -- and the golden retriever muscular dystrophy dog models of the disease. In these models, point mutations result in the absence of dystrophin, but efficacy will need to be improved in patients to lead to significant disease modification.
Just as the identification of the dystrophin gene was one of the first successes of positional cloning, the pioneering genetic approached now entering the clinic for DMD [TABLE 1] are also applicable to other diseases."
Now I've been able to preview page 1 (without buying the article). The paper is a fascinating write-up and goes over all kinds of interesting information. For example, it says that in Becker Muscular Dystrophy (BMD), the symptoms can range from "loss of ambulation in the late teens to manifestation only as a cardiomyopathy in patients who live into their 80s." If exon skipping can render DMD to behave like BMD, as we have heard from the scientists, then the benefit is potentially enormous.
Hopefully I can get the full article through my university when the print version comes out. Somehow my online access through the library isn't getting me full the article right now.
Author affiliations (note the Prosensa connection, which is OK!):
Rebecca J. Fairclough, Matthew J. Wood and Kay E. Davies are at the Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK.
Rebecca J. Fairclough and Kay E. Davies are also at the MRC Functional Genomics Unit, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, Parks Road, Oxford OX1 3PT, UK.
Competing interests statement
Kay E. Davies is on the scientific advisory board of Prosensa plc and Summit plc. Rebecca J. Fairclough and Matthew J. Wood declare no competing financial interests.
Cool! I was only able to get the abstract of the article so far (very promising for future treatment of **many other disorders**):
"Duchenne muscular dystrophy (DMD) is a devastating progressive disease for which there is currently no effective treatment except palliative therapy. There are several promising genetic approaches, including viral delivery of the missing dystrophin gene, read-through of translation stop codons, exon skipping to restore the reading frame and increased expression of the compensatory utrophin gene. The lessons learned from these approaches will be applicable to many other disorders."