to fall into place. The problem was that in the early days, people were a bit overly optimistic. There was too much hype. But progress is coming along. We have a mouse model for Duchenne Muscular Dystrophy, and using gene therapy, we are now able to cure those mice. That, in my view, is a major advancement, and we’re getting close to taking this into the clinic.
So there were early setbacks in gene therapy, but things are coming along. It’s a huge challenge to try to replace genes throughout the body. It was going to take longer than we anticipated.
X: OK, but there’s more than one way to try to accomplish this goal of getting the body to start expressing the dystrophin protein. What are some of the best techniques out there that get you excited, besides gene therapy?
JC: I’d say there are five approaches with tremendous potential to have an impact. One is gene therapy. Of the other approaches, the one that’s most developed is the stuff that AVI Biopharma is doing. What they’re trying to do is use small oligonucleotides to manipulate the processing of the dystrophin transcript as it comes off the gene. Basically, the antisense oligonucleotide technology has been shown to … essentially bypass the mutation.
The advantage of that technology is that it can be converted into an ingestible drug. Right now, they’re mostly giving it via injection, either intravenous or intramuscular. It has potential to even be orally administered. It seems simple, it can be given repeatedly, and so far in the animal models, it’s been shown to be fairly effective.
There’s a little bit of safety data now coming out from the human trials [published in The Lancet]. And there was another paper published with a slightly different approach published in the New England Journal of Medicine last year. So it’s showing a lot of promise, and will be an important technology.
There are some limitations to the antisense oligonucleotide technology. One, not every patient will be a candidate for that type of treatment. It depends on what kind of mutation they have. Certain mutations, I don’t think will be correctable. Fortunately, the majority of cases look like they will be treatable with this technology if it works.
The second concern is more of a long range concern that nobody really has answers to. That is, since this drug has a very short half-life. It probably needs to be given every two weeks, or every week, for the rest of the life of the patient. Nobody really knows what the long-term consequences of taking these will be. Will there be off-target effects that start to surface over the years, or will you introduce toxicity, or an immune reaction to [the drug] itself that would limit long-term use? So far, that’s purely a theoretical concern and nobody has seen evidence of that.
X: Can it be delivered throughout the body to every cell?
JC: Mostly, I should say. It appears
